Corneal Nerves by MikeJenny


									2/8–Corneal Nerves cornea most sensitive part of body                  This b/c corn nerves overlap @apex
   U can see nerves better in a kerataconic pt                         Touch most easily measured  touch threshold
   Nerves enter cornea radially (60-70 nerve trunks) –                 Mainly do touch and pain
    mostly myelinated, but…                                             A little temperature (corn is a little colder than body)
   Nerves lose myelin 1.5 mm upon entering cornea                      Touch thresh varies with race and eye pigment (see p
    (through limbus)                                                     82 chart)
   Nerves enter cornea 2 ways:                                       After 8 hrs CL wear, touch thresh increases
     Short ciliary N – posterior, close to CN II                         Hypoxia  reduced sensitivity
     Long cil. N – enter more horizontally and anteriorly                           Change in touch threshold
     Cil. N cont. in suprachoroid layer and the superior                                  (mgm/mm^2)
         aspect of cil. body.                                                        Lens       Before       After
     Fibers enter cornea radially and branch twd apex.                                         insert       insert
     Corn. N in 2/3 of cornea.                                                    Hard        20            45
     Use peptidergic and classical neurotransmitters.                             Soft        20            30
    Normal thrshold = 40 mgm/mm^2                                    Sensitivity decreases with age (p 82 chart)
   CL thrshold = 80 mgm/mm^2 (less sensitive)                      2 terminal types:
   F(n)s                                                             simple – few mito.
     Defense                                                             Form small consecutive dilations along their
     Trophic – loss of corn. N.  neuroparalytic keratitis                   fibers
         (there’s a struc. Relationship b/w epith cells and               Found very close to base membr
         nerves. Damage to nerves damages the cells)                  Large – (.5-2 um)
   Origin: (sensory)                                                     Much mito.
     CN V-1 (mainly)                                            Sclera
     CN V-2 (?)                                                    Largest part in fibrous tunic (outer coat) = 5/6-9/10
   2 plexi (pic p. 81)                                             Tendon’s capsule – dense fib tiss that envelopes entire
     epith – most dense                                             eye (att to septum orbitales)
          are deep in epi in basal cells                           F(n)s
          allow trauma w/o sensation (trauma thresh <                Protect intraocular parts
              sens thrsh)                                             Maintain overall shape of eye
          mainly in basal cells, very few single axons go to       Embryology
              squamous layer                                          Mesoderm (like stroma and endo of cornea)
     stroma – 2nd line of defense                                    Clear embryo tissue (like all)
          end close to epi                                           Becomes opaque right before birth
          respond to anterior stimuli                                In new borns – bluish (almost translucent) b/c so
     in center of corn, little communication b/c 2 plexi!                delicate
         (see pic p. 83)                                              But soon becomes white and opaque
     ramus perforan – sm nerve br. that go from stroma               Healthy cornea – clear all life
         into epi, crossing ALL.                                      Sclera and corn different b/c diff ultrastr.
          Very few in central cornea                                 Ant part of sclera made first during embryogenesis so
          So 2 plexi are mostly inde.                                    EOM can insert
   3 fiber types:                                                    Limbus originally lying over cil body, but moves fwd
     myelin – in PNS                                                     later
          have schwann cell and mye insulation                       Tenon’s capsule encases globe and joins septum
          lose mye after 1.5 mm into limbus                              orbitale
     non-myelin – in corneal stroma                                       Dev like sclera, but later
          have schwann cell and NO mye                             Structure:
          when nerves lost mye sheath  non-mye                      Males thicker than fem
     naked – epith. N. ALL naked                                     Thickest at post pole (1-1.35mm) and decreases twd
          no schwann and no mye                                          equator
          epi nerves are wrapped in infolding of epi. cells          Min thick is under rect musc tendons (0.3mm)
              that act as schwann cells in unmye bundle
                                                                      Tendons thick = sclera  0.6 mm together
          epith nerves have free, unspecialized nerve
                                                                      Then, sclera increases thickness twd limbus
              endings (unlike skin)
          epith n endings have beaded swellings.
                                                                      Ext diameter of globe 23-25mm, wider horiz, but
   Corn. Nerves sensitive to >1 stimulus type
                                                                          varies w/ sex, race, and Rx
     Corn sensitivity is the best measure of corn health
                                                                    3 regions: all the same morphology, but diff ultrastruct.
         (use corn aesthesiometer)
                                                                     Sclera NOT truly layered…for convenience
     Apex of corn most sensitive, then decreases radially,
                                                                      all layers – conn tiss = a lot of collagen and some
         decreases into conj, increase @ fornix and lid margin
                                                                          elastin prot
         (near cornea)
                                                                           episclera
            scleral stroma – corneal stroma is only layer that       Short post cil arteries – in a ring around optic disc =
             cont w/ sclera                                               annulus of Zinn
         lamina fusca                                                     8-20 in #
   Episclera (pic 95-97)                                                  short post cil nerves usually enter eye w/ the
     Ant to stroma                                                            short post cil Art, but sometimes, N or Art come
     Less compact and more vascular that stroma                               alone
     Its vascular, but Tenon’s capsule (also coll) - avasc                sometimes, they enter eye through dura mater of
     Thicker anteriorly and gets thinner post to rect musc                    opt N.
        att                                                           Long post cil art and nerves
     In anterior, att to conj.                                            Pierce more anteriorly and usually along
     Bulk is made of small bundles of collagen fibrils w/                     horizont meridians (but not always)
        some fibrocytes and melanocytes                                    Art and nerves usually enter together
     Coll fib have med diameter (50-60 nm)                           Vortex veins
     Diam and spacing of coll fibers pretty uniform, but                  Usually 4 (but not always)
        not as uniform as stroma                                           4mm post to equator
                                                                           go from choroid and drains uvea
     Has some med size elastin fib
                                                                      Ant cil veins and arts
     Bl vess are from Ant (provides ant side) and Post
                                                                           Anterior to equator
        (provides post side) Cil Art
                                                                           Branches from muscular art that supply EOMs
   Scleral Stroma = substantia propria
                                                                           Ant cil art are 3mm peripheral to limbal region
     Made of dense bundles of coll fib and few sclerocytes
                                                                               (7 in #)
        (sim to keratocytes of corneal stroma)
                                                                           Supply anterior uvea and episclera
     Components = corn stroma, but diff structure  corn
                                                                      Canal of Schlemm
        clear, sclera not
                                                                           Annular course w/in limbal region of the outer
     Sclera = coll bundles not in uniform flat sheets of                      coat
        lamellae                                                           Also communicates internally w/ ant chamber
         Bundles irregular and undulating, esp when                           via trabeculum
             bundles are flatter (like in mid-stroma)                      NOT connected to ant chamb
         Coll fib no have uniform diam and spacing                        Externally comm w/ ant veins which drain the
         Coll fib diam vary with depth                                        eye via collector channels.
         Diameters most variable @ at mid-sclera (50nm-                   Some coll channels = aq veins b/c take aq from
             400nm) opaque                                                    canal to conj
         Lg fibers scatter light (unlike cornea)
         Sclerocytes are few, so no formal j(n)s and not
                                                                  Limbus – where cornea meets sclera (and conj)
             enough to make regular coll fibers                    1 mm wide – clinically a transitional zone, but defined
         Deeper in stroma, and esp more posteriorly and             histologically
             near rect musc, some netwk of elastin fib weave       3 f(n)s
             b/w coll bundles                                         nourish peripheral cornea
   Lamina Fusca                                                      provide outflow for aq humor
     Modified internal stroma                                        assist in corn epith regeneration
     Here many melanocytes (migrated from choroid)                some corn layers end, some are modified and continue on
     Fibr conn tiss here more loose than in stroma                  to sclera and conj
     B/c pigment – looks like suprachoroid                        limbal epith has stem cells for corn regeneration
   Penetrations of sclera (pic p. 98)                             corn endoth modifies  trabecular mesh : impo in IOP
     Bl vess and nerves                                             and glaucoma
     Largest penetration – optic N – nasal and sup to post        Epithelium
        pole                                                          Cont w/ cornea but modified
         Lamina cribrosa = sieve in sclera @ opt N where             Cornea cont with conj
             ganglion axons pass                                      Has stem cells
         As gang axons pass, become myelin  increase                Here, epi become thicker and less regular
             in opt N diameter                                        At least 10 layers , mainly more wing cells in corn
         This makes opening a cone shape, with internal                  epith
             diam=1.5-2.0mm, ext diam = 3.0-3.5mm                     Basal cells smaller and more dense pack, but still 1
         Lamina cribosa = weakest part of sclera and gets                layer
             pushed back in glaucoma                                  Base membr on post side continues into conj
         High IOP w/ glaucoma  lamina cribrosa                           In limbus, base memb in undulating and not as
             cupping                                                           flast as corn
         Ischemic changes of ONH also  cupping                           In conj, epi thickness decreases to 3-4 layers,
         Also pallor show capill to ONH dmged -->                             except in Palisades of Vogt (epi ridges with huge
             ischemic                                                          stock piles)
         So optic disc anat (C/D) impo sign in glaucoma              Some pigment in basal cells due to melanin granules
             (which can blind you!)                                       from conj
     Blue eyes less pigment in limbus than dark color eyes                  Apex of triangle is the termination of PLL =
     NO goblet cells in limbal epith (but are in conj epith)                 Schwalbe’s ring (mesh has 3-5 layers)
     In ultrastruct, cornea and limbal epith cells similar              Base is scleral spur and cil musc origin (mesh
   ALL (bowman’s membr)                                                      has 15-20 layers)
     Stops at periph cornea to mark limit of cornea                     Endoth cells make strands, 40 um long, 4-5 um
   Stroma                                                                    thick except where nucleus is
                                                                         Has uveal and corneoscleral part – both same
     Cornea cont with sclera, but loses regularity
                                                                              composition, but diff a little diff shape
     Limbus stroma loses some clearness but not yet                           Corneoscl – larger, external, 3 layers
                                                                                   (strands), forms flat sheets in cross-section
                                                                               Uveal – forms cords in cross-section
     Lose clearness b/c coll fiber diam and spacing more
        varied                                                      There are actin filaments in endo cells of trab and
                                                                        canal. So maybe endo cells can contract. Filaments
     Also have limbal loops – bl vess b/w coll bundles.
                                                                        also help form macrovacuole.
        No become filled till eyes irritated. Come from ant
        cil art. In conj.                                           Some controversy in how schlemm canal and ant
                                                                        chamber communicate:
   PLL (descemets membr)
                                                                         Sondermann – internal collector channels
     In cornea, not in sclera
                                                                              connect ant chamber w/ canal. (channels called
     Outer line of corn PLL makes ring boundary that you
                                                                              canal of Sondermann)
        can see w/ gonioscope = Schwalbe’s ring
                                                                         But some people say there no channels, just
     But base membr of endoth cells DO cont at a more                        spaces. Schlemm’s canal has small divertions,
        typical thickness (thinner)                                           but they no reach ant chamber
 2/17                                                                   Up to now, no one can show that the diversions
   Endothelium – become trab mesh @ limbus!!                                 connect ant chamber w/ canal. The extensions
     Cont with cornea, but changes to allow aq humor                         prob just increase surface area of canal inner
       outflow (if blocked, IOP increase  hurt CN II                        wall.
       glaucoma)                                                         So Sondermanns canals are just spaces for SA
     Aq flow: ant chamber trab mesh  canal of                    There is no continuous membr across the trabec.
       Schlemm  collector channels (aq veins) venous                   Aq flows b/w holes in mesh to canal of schlemm
       sys                                                                    by IOP. (IOP also helps macrovacuoles). So
     Friedrich Schlemm first saw canal of Schlemm in                         macrovacuole process is passive (no NRG
       dead hung criminal…filled with blood  named it                        needed)
       “sinus venosus” and people thought it was a vein             Aq leaves schlemm canal via 25-35 collector
       till…                                                            channels from ext wall of canal.
     Troncoso used gonioscope to show it’s usually                 These channels = veins that join deep scleral plexus
       aqueous fluid. So the canal of schlemm NOT a vein                directly or pass to eye surface as aq veins.
       in f(n) though it’s struct is similar                        Aq veins join episcleral vein, blood may get diluted
     Schlemms canal:                                                   or the aq and blood run unmixed side-by-side in a
        Annular channel at corneoscleral j(n) close to                 laminated vessel.
            scleral spur                                            Aq vein - .01-.1 mm, is lined w/ endo, and the CT of
        Diam = 0.3 mm                                                  wall of schlemm canal is continuous w/ aq veins.
        Formed by endoth cells whose nuclei near lumen             Collector channels also drain into the venous plexi of
        Endoth cells join by continuous tite j(n)s                     cil body and conj.
        Sometimes the canal is duplicated, but rare                The rabbit is mainly used as ophthalmic animal
        Thin layer of CT surrounds the endoth tube                     model.
            lining the canal                                             It has complete endo coverage of trab meshes.
        CT = fibrocytes and coll fibers                                 This peripheral extension of corn endoth forces
        In lower animals, some sm musc cells near canal                      aq to first move through this layer of cells before
        Endoth lining of (posterior) internal wall of canal                  flowing b/w meshes to canal.
            have lg cytoplasm vesicles = macrovacuoles (15               No know what controls this transendothelial flow
            um diam)                                                     Chaudler’s syndrome – endo layer not in lumen -
        These bring aq from trab mesh through endoth                          glaucoma
            cells into canal                                    Trabeculum (see p 103 and 104)
        Some aq also diffuses passively through cell            Modified corn endoth b/w periphery of cornea and angle
            walls of canal too                                     recess
        Macrovac maybe more for lg molec and
                                                                 Made of branching sheets of fenestrated CT
                                                                 Communicates ant chamb w/ Schlemm canal
     Trabeculae
                                                                 Schlemm canal is anterior (external) to trab in internal
        B/w canal and ant chamber
                                                                   scleral sulcus
        Strands of coll, endoth, elast fibers
        Thicker at base  triangle shape                        Its at filtration angle (need gonio lens b/w hidden)
                                                                 If angle is too narrow, may not see some parts
   If no see trabeculum, don’t dilate!                               Weird: trab mesh is greatest resistance to flow even
   Must see trab in 25% of ring to dilate ok                             though it’s freely filtered (80% Aq filters through
   In gonioscopy view, ant post                                         trab)
     Schwalbe’s line – dense ring of coll and elastic tiss at             Trab only let particles under 1-2.5 um diameter
         lateral limit of PLL (may not see)                                    pass resistance to outflow
     Trab mesh – may be brown if pigment is trapped                       If dissect trab, lose most of resistance
          If you don’t see trab, don’t dilate!                            In glaucoma surgery, cut trab to reduce IOP.
     Canal of Schlemm – peripheral and anterior to trab.             Endoth cells lining schlem canal are the first
          May be red if blood backflows from veins, but                  membran aq must cross and are the final barrier to
              usually clear and hard to see                               flow (5% of resistance)
     Scleral spur – internal projection of sclera, made of           Lumen of canal of schlemm is made by endo cells w/
         condensed stroma tissue w/ dense coll bundles                    a surrounding base memb. Thin layer of CT
          Seen as white ring                                             surrounds canal = tunica adventitia.
     Ciliary body – most peripheral and posterior (inner)            Fluid passes through endo via 4 ways:
         structure                                                         Macrovacuoles – most impo. Passive (no NRG).
          Densely pigmented                                                   Made on basal side of cell, forms aq filled space,
     Iris (not really in angle, but 6th structure in view)                    cause apical endo cell membran to burst and
   Iris processes = pectinate ligaments – bridges the angle of                expel aq. (through cell)
    ant chamb                                                              Flow b/w endo cells – tiny b/c tite j(n)s = zon
     Insert twd angle recess usually, but sometimes, they                     occludens
                                                                           Active transport across endo cells via small
         extend fwd to midpart of trab
                                                                               pinocytic vesicles – very small
     Uveal origin
                                                                           IOP pushes from ant cham to canal to venous
     From anterior iris stroma – has same morphology
         (coll, melanocytes, fibroblasts)
                                                                      Canal of schlemm is NOT a vein, although blood can
     Merge w/ trab mesh and develop the morphology of
                                                                          backflow b/c no valves
         uveal cords, losing melanocytes and fibroblasts
                                                                      Aq also drains via uveoscleral pathway:
   Trab = triangle:
                                                                           No membranes cause resistance
     Apex (anterior and thin) – Schwalbe’s line (PLL)                     Passively drains 10-15% of aq
     Base (post and thick) – scleral spur and ant surface of              Aq to directly into cil body, and is eventually
         ciliary body (which lies internal to spur)                            absorbed by veins of cil musc, suprachoroidal
     Outer (ant) side – faces corneoscleral stroma and                        space, vortex veins, and choroidal circulation
         schlemm’s canal                                                   Uveoscleral outflow reduces some w/ age
     Inner (post) side – ant chamb                               Uvea – middle layer (uva =grape in grk)
   Has 2 separate tissues: trab is just CT in the middle of 2     3 parts: all continuous, but w/ diff f(n)s
    endo cells…disease can spread b/w the 2 coats below
                                                                      Choroid
     Corneoscleral meshwork – outer part – 30-40 meshes
                                                                      Ciliary body
          Flattened sheets that branch and interlace w/
                                                                      Iris
          Each sheet has perforated pores to let aq flow          Much bl vess and nerves and pigmented
              from ant cham to canal of schlemm                    Embryology
          Each sheet has 4 parts:                                    Mesodermal and neuroectodermal
               Coll fibers and some fibrocytes                       Choroid:
               Elastic fibers                                             Visible after 4-5 wks
               Basement membrane                                          Mesoderm
               Endothelium                                           Ciliary body:
                                                                           Visible after 3 months
     Uveal meshwork – inner part – 5-7 meshes
                                                                           Mainly mesoderm
          Cord-like w/ wide passages
                                                                           Inner part – neuroectoderm
          Cords are covered by endo containing the same 4
              components as corneoscleral sheets.                     Iris
                                                                           Stroma mesoderm
   Aq Humor flow 2 ways: canal of schlemm and
                                                                           Posteriorly, 2 pigmented epith layers – neuroecto
    uveoscleral way
                                                                           2 muscles – sphincter & dilator – neuroectoderm
     Come from bl vessels in cil body processes
                                                                  Choroid – p 112-113
     Exits via cil body, episcleral and conj vessels to
                                                                      Thin, soft, brown coat
                                                                      Lines internal sclera and external retina
     Cil body  post cham  b/w lens and iris (pupil) 
                                                                      Covers all post eye (extends from opt N to cil body)
         ant cham  trab mesh  canal of Schlemm 
         collector channels  aq veins.                               Very vascular -->erectile tiss
     Aq moves from ant chamb to canal of schlemm w/o                 Thickest part @ post pole
         crossing a membrane (trab is NOT a cont membr)               Pigment, melanocytes, fibrobl, coll bundles
 Gives fundus its appearance. Tigroid = striated due                     Art and artles have sm musc cells in walls,
  to pigment b/w vessels                                                   but artl musc wall is incomplete (has holes)
   Art - cont sm musc, artole - holes in sm musc                   Basal lamina = bruch’s membrane
   Both are dually ANS innervated in the choroid                       Forms choroidal att to retina
 In white peo, RPE few pigment, can see through to                     In retinal detach, all of retina except RPE
  choroids (neural retina is clear)                                        detach b/c RPE stronger to choroids than to
 Choroidal nevus – pigment @ birth (freckle)                              neural retina
 Functions                                                             External elastic part – perforated,
   Nutrition to outer retina (inner retina nutrition by                   fenestrated so capill can feed retina and
       retinal blood circulation)…metabolites                              remove waste
   Moves waste from outer retina                                       internal cuticular part - collagenous
        natural receptor cell removal process                          Elastic part has fenestrations to aid flow of
        receptor renewal process                                          metabolites from choriocapillaris
        outer part of cell  RPE  blood stream                        Promotes retinal nutr and waste removal
        neural retina = clear; RPE = pigmented, but                    Thickens w/ age 135% in 100 yrs. But this
            in white people, few pigment, can see more                     thickening no related to macular degen
            of choroids                                                 External to this layer is choroidal stroma
        drusen – white leaks from choroids to retina           Bl supply – get para and symp innervation
   Allows passage of nerves and vessels to anterior                Long post cil art (2)
       eye. (vessels are lg and fill up choroid space)              Short post cil art (15-20) – enter horizontally
   Absorbs light (b/c pigmented) that retina no                    Choriocapillaries
       absorbs                                                      Ant cil art (7) – supply anterior choroids
 Structure - 3 (4?) layers: - p 115                                Vortex veins (4…or more) – in quadrants.
   Suprachoroid - external                                            Upper hemispheres no comm. w/ lower hemi.
        Very thin                                                     Drains WHOLE choroid
        There are thin attachments b/w sclera and              Nerve supply
            suprachoroid.                                           Choroid gets NO sensory innerv. Bl gets nerv
        Melanocytes in this layer send out processes               Long and short cil n – move anteriorly in
            which have lamellar arrangement.                           suprachoroid and give sm branches to choroidal
        Melanocytes have pigment, but fibrocyte                       vasculature. They carry para and symp nerves
            processes no pigment                                    Rami ocularis – para from CN VII pterygopal
        Coll fibers are sparse                                        ganglion
        Nerve fiber bundles unmye                                      Innervate arterioles of choroids
        Bl vessels dually innerv by ANS (art,                          Para stim  vasodilation and increase blood
            artless, veins)                                         Sympathetic – come in the short cil n w/ bl vess.
        No sensory innerv in choroids                                  Stim  vasoconstriction
   Stroma??                                                        Ganglion cells – infrequently found in choroids
   Vascular layers (3) – feed retina, not choroids!                    Multipolar cells (so they’re autonomic
        Haller’s layer – lg vessels, ext                                  motor neurons to sm musc in choroid)
        Sattlers layer – sm vessels, int. sm b/c of                    Mult contacts w/ other cells
            branching                                         Tapetan Lucidum – cause eye reflection in cats, fish, etc
        Choriocapillaris – matting against retina              Series of cells w/ reflective rods line retina
            red fundus                                         Few metabolism and bl vess
             Some of the largest capill in body                So fish can see in water, cat see at nite, etc
             Impo to retina - fenestrated                      Choriocapill feed retina, not choroidal cells
             Very permeable compared to retinal           2/22 Ciliary Body
                 vessels                                    Middle struct of uvea
             Has dense pattern of fenestrations, esp         Mesoderm and neuroectoderm
                 on retinal side                              Begins in 3rd month of pregnancy
             Not innerv                                      Not fully dev till after birth
             Maintain a high pressure to resist              Ant – cont w/ iris (border = scleral spur)
                 collapse from high IOP                       Post – cont w/ choroids and retina (border = ora serrata)
             Density of choriocap decreases w/ age           Ora serrata = ant limit of retina
             In 10 decades, capill dense reduces by          Ant sclera is outside of it
                 45%, and even more in macular degen
                                                              6 mm wide
                 (lose much bl supply.
                                                              2 regions:
        Art are branches of short post cil art
                                                                Pars Plicata = corona ciliaris
        Veins converge  4 (or more) vortex veins
                                                                     Ridged, elevated, ant part
            which pierce sclera and join ophth veins
                                                                     Ciliary processes = deep invaginations,
                                                                        organized radially, to increase SA to make aq
            Very vascular and fenestrated capill  aq                   Has much bl vess and nerves (fen capill)
            Vessels have high internal pressure so no                   Pigmented
             collapse                                                Cil body epith – 2 layers sandwiched b/w 2 base
         Aq secreted to post chamb                                     membr
         Little conn tiss in cil proc b/c block aq flow                 Pigment epith (external row, next to stroma)
     Pars Plana = orbicularis ciliaris                                       Basement memb faces stroma
         Post part                                                           Cont w/ RPE (get pigment from RPE which
         Cont w/ choroids and retina                                             moves twd iris)
         Epith cells cont w/ retinal epith cells                             Cont w/ iris ant epith (some pigment)
         Ora serrata = j(n) b/w cil body and retina                     Ciliary epith (internal row, next to post chamb)
   Functions                                                                 Base membr faces post chamb = internal
     Make aq humor                                                               limiting membr – cont from iris to CN II
     Accommodation                                                           No pigment
         Relaxes zonules  lens curve more                                   Near capill, epith modified for nutr flow
         Constricts pupil                                                        from vessels
     Absorbs light via pigmentation  decrease scattering                    Much organelles (ER, mito = much meta)
         better retinal img                                                  Specialized for aq prod
   Layers (out to in)                                                        Much interdigitations b/w cells in this layer
     Suprachoroidal space/supraciliaris lamina                               Cont w/ neural retina
     Ciliary muscle (1 musc, 3 fibers) – bulk of cil body                    Cont w/ iris post pig epith
             sm musc                                                         P 116 know cell j(n)s!!!!
         Meridional fibers (longitudinal) – the bulk            J(n)s                  F(n)s            Location
              parallel to outer coat                            Desmo                  Att cells.       B/w pig epith
              most external (closest to sclera)                 (mac adh)              Some move ok B/w nonpig ep
              go from scl spur in trab to pars plana                                                    B/w pig & nonpig
              when accom, cil musc contracts --> pulls          Gap                    Ion commun       B/w pig epith
                  sceral spur -->enlarges trab --> dec IOP                                               B/w nonpig ep
         Radial fibers – oblique and radiate out from                                                   B/w pig & nonpig
             scleral spur                                        Intermed jn                             B/w nonpig ep
              The middle layer of musc                          (zon adh)                               B/w pig & nonpig
         Circular fibers – annular and sphincter action.        Tite                   No let fluid go B/w nonpig ep
              Most internal                                     (zon occl)             b/w cells
         All musc highly vascularized                           Zonule (susp lig)                       B/w cil body & iris
         Largest smooth musc in eye
         Bulk of cil body (pwrful)                                 Blood supply – ciliary sys - art and artoles have dual ANS
         Att to scleral spur                                       Nerve
         Controls pwr of lens by contracting and relazing
                                                                      Para – CN III
             zonules --> change lens shape                                Midbrn --> pregang --> sup orb fissure --> cil
         Much ANS innerv                                                    gang --> postgang --> short cil nerves -->enter
         Much mito (much meta)                                              eye near post pole and around CN II
         Desmosomes to contract uniformily                               Most of these short cil n fibers go to cil musc
         Gap j(n)s to comm                                               Long post cil n run horiz
         Fibers titely packed
                                                                          Short post cil n run vert
         More fibrobl near scl spur --> more CT to attatch
                                                                      Symp – inhibitory
         Basement membrane around the cell except
                                                                          Debated (1% of terminals are symp)
             where desmosome and gap j(n)s are
                                                                          Cil bl vessels do get symp
         Myofilaments = contractile elements of musc
                                                                      Para – CN VII – to cil bl vess
         Pinocytotic vesicles help fluid uptake
         Much endo reticulum                                         Multipol ganglion cells – origin and f(n) unknown
         Some pigment in musc, but not in indiv fibers               Sensory – p 170
         Nerve terminals lose their Schwann cell                         From CN V go mainly to cornea
             wrapping at pt of termination                                Essentially none to choroids
         Diffuse innerv lets 1 nerve innerv many fibers                  Essentially none to iris
         Musc cell memb has receptors for NT                             Some to cil body
         Nerve cells were recently found in cil musc                     20% of unmye n in cil body are sensory (in loose
              in radial and circular fibers                                 stroma near angle recess)
                                                                          maybe they monitor IOP so brain can fix IOP
              stained (+) for nitric oxide
              synapsed w/ unmye fibers                          Aqueous Humor
              proposal – these neurons are in the                  Functions
                  fluctuations of accom during steady fixation        Main way to keep IOP
     Ciliary body stroma                                             Nourishes entire lens and part of cornea.
          Impo in transparency                                   Iris (p120-123)
   Fills ant (0.25 ml in man) and post cham (0.06 ml)               No 2 are alike (not even OD and OS or twins)
   Refr ind tiny lower than cornea’s --> low pwr diverge lens       Fingerprint
   Main diff b/w aq and plasma is low prot conc                     Iridology – science that says if you look at iris, you can
     Aq – 5-16mg/100ml in man                                        determine all ailments in body…no proof.
     Plasma – 6000-7000mg/100ml in man                              Origin
     Protein – colloid b/c molec lg enough to scatter lt              Ant stroma – mesoderm
     Non-colloids are dissolved solids -->clear soln                  Bron says stroma is mesenchymal due to neural crest
     So no good if colloids in aq                                         cells
   Bl-Aq Barrier – p 116                                              2 post epith rows – neuroectodermal
     Choriocapill --> Aq by cil epith of cil processes -->          Function
         post chamb --> ant chamb --> drains at filtration             Diaphragm controls pupil size and amt lt into eye
         angle --> Sch canal                                           pigment no let lite enter eye outside of pupil
     Capill in cil process = lgest in body (up to 45 um)            Gross appearance
     Stroma of cil thin -->little resistance to aq flow               Most ant struct of uvea
     We no know much of how base memb affect aq flow                  Diam – 12 mm
     Bl elements go across cil epith cells-2 ways possible            Circumference – 38mm
          Through cells                                               Thickest at collarette (0.6 mm)
          B/w cells                                                   Thinnest at root (0.5mm)
     3 Theories of what dictates movement across barrier              Must use gonio lens to see periphery (att to cil body)
          Diffusion – gas/liq molec continous passively               Visible iris diam is used clinically to meas corn diam
              move twd epith                                               for CL diam
               Maybe diffuse across a biological membr                Stroma tiss – ant
               No NRG used                                            2 layers of densly pig epith cells – post
          Dialysis – selective movement of electrolytes
                                                                       pupil tiny inf and nasal to geo center and regulates
              across membr
                                                                           amt lt into eye
               Ex – if membr perm to salt and water, but
                                                                       pupil diam – 1.5-8 mm in youth
                   not protein, salt diffuse across, but water
                                                                       old peo – avg pup size smaller due to:
                   from other side move to protein side
                                                                                fibrotic changes in sphincter
               Gibbs – Donnan equil
                                                                            atrophy of dilator
                    [Na]x[Cl] = on both sides of membr
                                                                     Color and pigmentation
                    amt of Na on a side = Cl + prot ions of
                                                                       Color det by melanocytes in stroma and ant border
                        same side
          Secretion – there’s no synthesis of new subst
                                                                       Melanocytes have melanin, the only pigment in eye
               In active trans, use NRG to produce secreted
                                                                       Melanin is brown
                   subst (which is NOT new subst)
          At one time, peo think aq = ultrafilt of blood =            Brown iris – melanocytes are perfused and well pigm
              combo of diff, dialysis, and hydrostat press, but        Blue iris – less melanocytes
              not secretion. But Davson (1949) and Levene                   Very delicate and fine stroma scatters blue lt
              (1958) showed there’s not equilibrium b/w                     Longer wavelengths are absorbed
              plasma and aq, so can’t be ultrafiltrate or                   Shorter wavelengths (blue) are reflected by back
              dialysate. Instead, aq has more NaCl than                         scatter
              plasma                                                   Green iris – combo of blue and brown
          Now we believe in Secretion-Diffusion theory                Albino iris – buff color b/c no pigm melanocytes
               Kinsey and Reddy (1964) research                            Lt increase --> iris looks pink b/c lt across sclera
               70% Na in post cham enters by act trans                         transillumnates iris from behind.
               sm amt Cl also act trans to post chamb                 Collarette – thickest part of iris – p125
               the rest of Na and Cl come by pass diff                     1.6 mm from pupil margin
                                                                            divides surface --> papillary and ciliary zone (2
               Na act trans by cil epith need NRG, much
                                                                                zones differ in color)
                   mito in cil epith
                                                                            collarette overlies an incomplete vascular circle
               If you metabolic poisons, rate of aq
                                                                                = circulus vasculosus iridis minor (maj iridic art
                   formation decrease by 70-80%
                                                                                circle is in cil body…vessels from maj circle
               Rest of 20-30% come from ultra-filtration                       come in radially and anast to form minor circ.)
                   across bl-aq barrier                                     radial/concentric contraction folds in ciliary zone
               Aq made continuously at 2.8uL/min                      Fuch’s crypts
               W/ aging, 2.4uL/min                                         Ant iris surface has trabecular structure, esp in
               Importance of IOP and bl press on aq                            pupil and collarette area
                   formation unknown. But bl press at                       Superificial layer has discontinuities and pits =
                   capillary level must be greater than IOP if                  Fuch’s crypts
                   hydrost press helps aq form.                             Trabecular struct forms Fuchs
           Trab is remnant of obliterated vessels that passed        Mutate rods, but cones often die after rods die.
            to the pupil membr in embryo.                           PR – p 141
    Pupillary Ruff                                                   OS and IS layers
        Formed as the post epith layers extend fwd @                 Cones – high VA, color vision, light
            pupil margin                                                  highest concentration in fovea
        Crenations of ruff are from a fwd extension of               rods – dim light
            the radial folds of the post iris surface                     dominate periphery of FOV
        See crenations best during miosis (constrict)                    highest density 20o outside fovea
        More prominent in diabetic                                   cilia att OS and IS and acts as a supply channel for
Retina pics p143-145, charts on p 147, pics p 148-154                    prot and lipids from IS to OS
 Development                                                         OS has 2000 discs
    Optic vesicle (already present) invaginates in 4th               OS 230 A thick
       week --> opt cup                                               Have visual pig – opsins
    So 2 layers of neuroectoderm cells are joined at                 Rods – rhodopsins, cones opsins for long, med, short
       apices                                                            wavelengths
    Ext layer --> RPE (monolayer)                                    In rods:
    Inner layer --> neural retina. Final organization of                 New discs cont made by infolding cell membr @
       neur retina no finish till after birth                                 OS base, which displace overlying discs sclerally
    Init, bl to retina by hyaloid art.                                   Turnover of visual pigment in dogs = 6 days
    Retinal art and vein appear in 4th mo and replace                    80-90 new discs made each day, and a stack is
       hyaloid. Overtake finishes in 5th mo, but final adult                  replaced every 9-12 days (35X/yr) in rhesus
       retinal vessel pattern no end till after birth                         monkeys
    Opt n gets more mye in prox to dist direction, and at                New discs made though life
       birth, this process reaches beyond lamina cribosa                  Scleral end discs shed.
    Mye of fibers usu stop at this pt, but in some peo, this             Cones have similar process
       cont to after birth. In these peo, mye n fib are brt               In rats, rods shed more discs in first few hrs of
       white in red fundus. This continued medullation after                  daylt, and less during rest of day and nite. But, if
       birth no = congenital feature, though most peo say so                  no turn lt on, still same thing. So lt no induce
 Layers (out --> in)                                                         disc shed…it’s a daily rhythym.
    RPE                                                                  But some reports – constant lt or dkness chges
    PR out and in seg (OS and IS)                                            thesynchronous shedding of rod discs much
    ELM                                                              In rods, discs become detached from OS base
    ONL                                                              In cones, all discs att to outer cell membr
    OPL                                                              But this diff no affect shedding. Both cells shed
    INL                                                              There is an age-related receptor cell loss in retina
    IPL                                                              In dis like Age-related macular degen, shed faster -->
    GCL (ganglion cell layer)                                           vision loss
    NFL (Nerve fiber layer)                                        ELM
    IILM (int lim membrane)                                          Has perforations by PR
 RPE                                                                 Netting in flat section
    Cuboidal cells w/ 2 pigments                                     Not a true membr
        Melanin                                                      All made up desmo jns b/w muller fibers and PR
        Lipofuscin                                                   Muller cells have nucl in INL
    Att to choroids and divide from neural ret                           lg complx neuroglial cells
    Internally, OS of PR twd apical RPE, and externally                  stretch from ILM to ELM
       (basal) RPE has base membr                                         impo in brkdwn glutamate, homeostasis of ionic
                                                                              micro-envi, neuronal survival, store glycogen
    Function
        Remove water & keep ionic micro-envi                       ONL-22-50 um
        Nourish outer parts of retina                                PR cell bodies (nucl/cyto)
        Phagocytose det discs of PR OS                               Rod nucl – oval – 5.5um
    RPE delicate cyto extensions enclose shed discs of               Cone nucl – oval and lger – 5-7um
       rod OS, take into cyto, and brk them down                          Less heterochromatin and stain fainter than rod
    Retinitis pigmentosa (RP) – PR degenerate                      OPL – 2 um
    In rats, PR degenerate similar to human RP                       Axons of PR that contact dendrites of bipolar (BP)
    In rats, main site for this retinal dystrophy is in RPE             and horiz (H) cells
       which no eat discs of PR                                       Rod – spherules, cone – pedicles
    Usually, RP is due to mutations in                               2 types of cone-BP synapses
        rhodopsin (visual pig)                                           synaptic ribbon synapse
        other OS prot                                                         in OPL, seen w/ e- dense ribbon in presyn
        stage in phototransduction g-prot cascade in rods                         cytoplasm
                 syn vesicles have NT = glutamate around                        70% of all gang cells
                  ribbon                                                       parasol – broad dend tree
              there are mult postsyn processes in retina                        variable size and shape
              H processes – lateral, deeper in invag                            increase in # in periphery
              BP proc – central.                                                10% of all gang cells
              In cones, BP proc depol w/ lt                                small bistratified
              In triad syn, 2 diff H cells                                      get input from blue cone BP cells
              In rods, 2 dendrites from 2 rod BP cell depol                     10% of all gang cells
                  w/ lt. H cells are from H cell axon terminals      Nerve Fiber Layer 20-30 um @ opt disc
         Basal (flat) jns                                             Made of gang axons
              Simple contacts w/ thick surf membr on pre              Fibers radiate twd opt disc (p151) to make opt N
                  and post-syn sides                                   Becomes mye @ lamina cribosa
              Not conventional syn b/c no vesicles grp on             Fibers from periph are closer to RPE and ext opt N
                  pre side                                             Fibers from near opt N are closer to vitr and deep in
              BP cells of flat jns w/ cones hyperpol w/ lt                opt N
     H cells have wider process spread and contact more               The origin of a nerve fiber and its location w/in the
        PR than BP cells, so H cells do lateral interactions               NFL xpl the pattern of visual field loss asso w/ some
        and BP cells do vert from OPL --> IPL                              diseases
   INL                                                                For ex, glaucoma affects ext fibers first  lose
     Has H, BP, Muller, interplexiform, and amacrine cell                 periph FOV first
        bodies                                                         When lose temporal peripheral fibers,  arcuate field
     This layer is 8 nuclei deep in fovea and 5 deep at ora               loss w/ a nasal step b/c these fibers no cross
        serrata                                                            horizontal meridian
     Out to in: H, BP, muller, amacrine, interplexiform               B/c fibers no cross horiz merid, opt n prob  field
     Cell bodies of rod BP who syn w/ rods,                               loss that respects the horiz midline
         Diffuse cone BP syn w/ a lot of cones                      Interanal limiting membr (ILM) – 1-2um
         Midget BP syn w/ a few red or green cones on                 A real base membr, so its very diff from ELM (not
             only one cone in foveal regions                               made of muller cells)
   IPL – 18-36 um                                                     Absent in opt disc b/c mullers absent in opt disc
     Thicker than OPL                                                 Muller cells secrete ILM
     Where 2nd and 3rd order neurons meet                             Retinal glial cells:
     BP, amacrine, interplex, and ganglion cells syn                       Muller cells
     BP -->glutamate -->amacrine and gang dendrites                        Astrocytes – insulate vasculature from the neural
     Synaptic ribbons are only in BP terminals where post                      structures
        syn cells are                                                            Also surrounds to opt n fibers in the
         Pair of amacrine cell processes                                            prelaminar regions of ONH
         Gang cell dendrite and amacrine proc                              Perivascular glia - insulate vasculature from the
         Rarely 2 gang cell dend                                               neural structures
     Amacrine cells                                                        Microglia – phagocytes
         form much conventional syn w/ BP, gang, and                Modifications of Retina
             other amacrine cells                                      Fovea
         can interrelate adjacent areas of the retina and                  Retinal layers are excavated (removed)
             the direction of conduction can be both ways.                  Foveola – most center part
         This shows that a local feedback sys exists                            Has no rods or blue cones, so its blue-blind
         Release inhib NT GABA and glycine                                          (foveal tritanopea)
         A II (a spec amacr cell) links rod BP to ganglion                      Has 10,000 cones
             cells                                                               Cones much longer, thinner, more dense 
     Interplex cells                                                                VA increases
         Gets all of its input from amacr cells                                 Acts as concave mirror
         Connects IPL to OPL as a intraretinal centrifugal                      You can see reflex w/ ophthalmoscope
             path                                                           RPE and choriocapill are unchanged in fovea
         NT is dopamine                                                    Yellow pigment – xanthophil – thought to be in
   GCL                                                                         fovea
     1-2 cells thick (10-20 um) usually                                         Yellow filter that absorbs blue lt –
     @ macular region, 80um thick                                                   contributes to blue blindness
     gang cells are multipolar                                        Opt Disc – blind spot
     cyto is fibrillar and contains Nissel granules                        Only has nerve fibers and astrocytes (no PR)
     3 major gang cell types                                          Peripheral Retina
         midget – narrow dendrite tree                                     Near ora serrata, retina less devel
              the most comm ones in central retina                         Structure not as perfect as centerally
            General thinning and vacuoles shows that ora                    = an extension of the hya artery adventitia
             serrata is less resistant to tearing                           in adult, remnants of hya art =
         Vitreous traction @ vitr base  ret detachment                      Cloquets canal
         Gradual thinning of retina near serrata                                  space where hya art used to be
         This shows why ret detach usually begins near                            most distinct landmark of vitr.
             here                                                                  Runs from pat fossa to opt n
         2nd reason this area weak is the strong local att                        Where first vitr formed in eye
             b/w vitr base and retina                                         Bergmeister’s papillae – grey linear struct @
   Retinal Circulation                                                           opt N
     Outer retina – by fen choriocappill bl supply                           Mittendorf’s dot – inferonasal to post pole
     Inner retina – by retinal circulation (less perm than                       of lens
        choriocapp)                                                   Secondary vitr = vitr gel body
     Ophthal A central retinal A  enters center of opt                 First dev at end of 6th week
        N.                                                                Accelular
     @ Opt N, central retinal artery has well devel tunica               First appears b/w retina and post bl vessles of
        media w/ 6 layers of sm musc.                                        vasa hyaloidea profria
     Central retinal A gets symp and CN VII para                         ECM of type II coll
     As central retinal A leaves opt N, it branches and its              Pushes 1st vitr fwd and centrally
        musc is replaced by an incomplete layer of pericytes              Vitr gel body = j(n) b/w 1st and 2nd vitr
     The incomplete layer of contractile cells make these                By 3rd month, vitr gel body is seen anteriorly as a
        artoles, not arts                                                    line that extends from ant part of hyal art over
     Now we have 4 artoles – sup and inf nasal and temp                     the post part of lens
     These artoles  nonfen capill that reach INL                        This line b/w 1st and 2nd vitr  cloquets canal
     Venous circ drains  ophth V                                    Tertiary vitr = Zonular fibers from cryst lens
     Venous sys follows art counterparts                                 Some controversy about this name
     So they are venules, not veins                                      No evidence says zon fibers are from vitr (but
                                                                             they may be)
     Fovea is avasc, and totally needs choriocapill
     If choroids and retina no comm.  age rel mac              Vitreous Composition
        degen, a leading cause of blindness in U.S.             Water               About 99% (98.5-99.7%)
                                                                Na                  137 mmol/kg water (less than aqeous)
                                                                K                   3.8              “”
See Dr. Frishman’s Aq Humor and Retina
                                                                Cl                  112.8           “”
       (3 lectures)                                             Bicarbonate         19.6-32.4 mEq/kg water
See Dr. Glasser’s Accomodation (1 lect)                         Glucose             30-70 mg/100ml water
                                                                Lactic acid         70
Vitreous – see pic p137                                         Pyruvic acid        7.3
   Largest organ of eye = 80% vol                              Citrate             1.9
   Gel body – mix of coll, water, HA                           Amino Acids         At 1/5 the concentration found in plasma
   15-16 mm long                                               Main Coll type      II
   lines the internal cil body, retina, and post lens          Other Coll types IV and IX
   n = 1.3349 (similar to water)                                Vitr Cortex – outer vitr
   transmits 90% light in 300-1400 nm                                Denser coll than inner vitr
   no absorbs UVA or UVB                                             Thickness = 200 um
   98.5% water                                                       thicker at ant suface next to cil body
   made of collagen                                                  thinner at post surface next to retina
   in young adult, 80% gel, 20% water                                not present over opt disc
   Origin: 3struct: diff origin                                      thins out over the macula
     primary vitreous = cellular                                3 vitr att
          first see in 3rd – 4th week                                vitr base = at ora serrata
          neural ectoderm separates from surface ectoderm                att to base membr of pars plana epith
          mesodermal cells enter vitr space by fetal fissure             att to inner lim membr of retina
          mesoderm cells  hyaloid artery                                strongest att!!
               branches of hyaloid art = vasa hyaloidea                  made by denser collagen netwk
                   propria                                                1.5 mm broad annular region
               same struct as arterioles in body                         some sources say that it’s peripheral to ora
               endoth tite j(n)s                                            serrata
                                                                          extends several mm in the vitr body itself
               adventitia around vessels have mononuclear
                   phagocytes and fibroblasts
                                                                          Peripheral retinal detachments occur here much
               fibrobl make collagen
                                                                             (here, retina is thinnest and most fragile)
               halocytes also make coll?                             Retrolental ligament of wieger
              Patellar fossa – where vitr hollows to fit lens             Vitr becomes more liquidy due to rearrangement of
              Retrolental space of Berger – space b/w lens and               collagen fibers
               patellar fossa (is it true space or an artifacet from       Age fibers less uniform  some fibers group 
               hist preparations?)                                            some areas become empty and fill w/ water
           Lig of wieger = annular 1-2 mm wide and 8-9                    Accumulation of water  collapse of vitr bag 
               mm diam                                                        posterior vitr detachment (PVD)
           Where ant vitr att to post lens                                    PVD = separation of post vitr cortex from ILM
     Opt n – much weaker than other 2                                             of retina
     Fovea – also much weaker                                                 Common in old eyes – affects 65% of peo over
 Cells in vitr                                                                    65 yrs old
     Hyalocytes – contain hyaluronic acid (HA)                                Doesn’t cause worse VA
           Make up 90% of vitr cells                                          Often causes floaters
               = macrophages (mononuclear)                                    If vitr doesn’t separate from the retina cleanly 
           w/in vitr cortex  cortex is the metabolic center                      tug on retina  retinal tear  liquid can leak
               of vitr                                                             from vitr to retina  retinal detachment
           oval shapes                                                EOMs – see p 51- 57, pics in class notes
           10-15 um diam                                               Eye has 3 intrinsic musc (tarsal, levator, orb oculi)
           have golgi, lobulated nucl, rER, sER,                          Sm musc inside eye
               phagosomes, and lysosomal granules                       7 extrinsic musc – all striated
           highest density near vitr base                                 2 extraocular rotary musc (EOM)
           med density near post pole                                     1 levator palp sup – elev lid
           lowest density @equator                                                           EOM and nerves
           posterior cells are flat and oval or spindle shaped              MR        CN III – inf division     Horiz move
           anterior cells are larger, round, or star shaped                 IO        CN III – inf division     Oblique move
           these cells are found where there’s much HA                      IR        CN III – inf division     Vert move
               concentration                                                 SR        CN III – sup division Vert move
           make HA in vitr                                                  SO        CN IV                     Oblique move
           contain enzymes needed for HA production                         LR        CN VI                     Horiz move
           help make glycoprot and collagen in vitr                         Lev       CN III – sup division
     Fibrocytes                                                             palp
           Along w/ glial cells, make up 10% of vitr cells
           Mainely w/in vitr base, near opt disc, and cil
                                                                          All EOMs (but IO) and levator orig in common tendinous
                                                                           annulus (of Zinn)
           Make collagen, esp during disease and injury
           No know if they make normal vitr coll                         EOM Structure
     Glial cells                                                           Striated and voluntary
           Structural cells                                                40 mm long
           In perimeter of vitr body                                       6-10 mm wide
           May be ectopic cells or other cells (fibrobl or                 recti m get bl and nerves on global (belly) side
               hyalocytes) that people mistake for glial cells              obl m get bl and nerves on orbital side
                                                                            origin is tendinous
 Vitr metabolism and f(n) - Vitr is meta active, although
                                                                            annulus of Zinn – made of dense, coll, CT
    it’s avascular
                                                                            insertion is tendinous (dense coll CT)
     Oxygen tension is lowest in central vitr (15.9 +/- 2.8
                                                                            EOM unique b/c most muscles orig and insert bone
          mm Hg)
                                                                            Levator has a long insertion (lid only has tendon, no
     Vitr is a metabolic respiratory for meta wastes and
                                                                               muscle fibers) that goes to skin
          short term retinal needs (allows waste and nutr
                                                                            Recti m insert into sclera, 5-7 mm post to limbus
          movement and stores nutr)
                                                                            Obl m insert post to equator
     Vitr is impo in moving solutes and solvents w/in eye.
                                                                            Endomysium wraps fibers
          50% of water is turned over in 10-15 min.
                                                                            Perimys wraps bundles
     Must maintain barrier to cell invasion to keep
                                                                            Epimys wraps whole musc
     Mechanical support for surrounding tissue                           EOM fibers – 2 types
     Viscoelastic properties: serves as a shock absorber.                  Extrafusal fibers – outside musc spindle, larger
                                                                            Intrafusal fibers- inside musc spindle, smaller
 Aging in the Vitr
                                                                            Musc spindles are afferent sensory organs, and are
              Aging in vitreous
                                                                               different in the EOMs than from other musc
  Age             % liquid             % gel                                Role of musc spind in eye not fully understood
 0-2 yrs              0                 100                                 Some species lack musc spind in EOMs
    2                 5                  95                                 Musc fibers – long, mutinucl cells
   25                20                  80                                 Filaments  fibrils  fibers  muscle
   65                60                  40                                 Filaments = basic contractile struct of striated musc

     Starting 2 yrs, vitr starts becoming more liquid
      Sarcoplasmic reticulum (ER) - in and among                                  EOM musc spind hasn’t dev to f(n) like rest
          filaments                                                                 of body
      Sarc retic responds to depol of sarcolemma and t-                        No know if EOM musc spind proprioceptive
          tubule sys by releasing Ca stores  contraction                           f(n) is at a reduced level of stretch reflex
      Tubular sys is made of tubular invaginations of                              sensitivity or has different a stretch reflex
          sarcolemma                                                                from other musc.
                   Fast vs Slow Twitch Fibers                                   20-80 musc spindles per EOM
Fast                              Slow                                     Golgi Tendon Organ
A lot of mito, ER                 Few mito, ER                                  Encapsulated sensory receptor deep in the
1 nerve                           cluster of nerves                                 tendon near the anterior musculotendinous
(en plaque innerv)                (en grappe innerv)                                j(n)
Fibrillen struktur                Feldern struktur                              One or more mye afferent axons enter organ
All-or-none                       Graded response                                   and end as a varicosity filled w/ mito and
Distinct bands                    Less distinct bands (diffuse)                     vesicles.
Dominate EOMs                     No dominates                                  These terminals are located b/w fine coll
                                                                                    tendon bundles.
     6 fiber types                                                             Provides feedback on muscle tension
          2 orbital fiber types – nearer the bony orbit                   Palisade Endings
               singly innerv fib (SIF) – fast                                  May be the most impo aff end organ of
               mult “ “ (MIF) – slow                                               EOMs
          4 global fiber types – near the globe (eyeball)                      Encapsulated w/ the muscle cell
               Red SIF                                                         Found in the myotendinous j(n) next to
               Intermed SIF                                                        global, MIF
               White SIF                                                       More common in the LR and MR
               MIF                                                             Involved in the stretch reflex.
   Aff Innerv of EOMs                                                     Spiral Nerve Endings
     If there’s no convergence among proprioceptive                            Wrap in a spiral around single musc fibers in
         nerve fibers, 10% of CN III is afferent                                    the belly and primarily around sm fibers
     Most of the aff fibers follow the motor nerve to                              along periphery
         brainstem                                                              Infrequent and not thought to be motor
     Only 1.38-3.7 % of nerve fibers have somata in                                endings to SIFs
         trigeminal ganglion (these are ophthalmic – CN V-I )      EOM Actions – if you know orig and inserts, you know
         and mainly unmye                                            actions of muscles
     Sensory organs in EOMs – we don’t really                        SR
         understand all the details                                        Runs parallel w/ line of orbit = 23 deg out
          The eye need very fine control…different from                   23 deg to the visual axis when eye looks straight
              skeletal musc of the body (great proprioception)             1st action – when eyes are turned 23 deg out 
          Muscle Spindles                                                     SR is the ONLY elevator
               Diff from musc spind from rest of body                     When eye looks straight:
               Encapsulated end organs containing 5                            2nd action - rotates top of eye twd nose
                  striated musc fibers                                              (incycloduction or intorsion)
               Seen in human EOMs since late 1800s                             3rd actions - pulls eye inwards (adduction)
               Not in some animals (rabbit)                          IR
               In ant and post 1/3 of musc (not in belly)            LR and MR – only musc w/ pure actions
               Contain 1-15 (avg 4) intrafusal fibers housed         SO – orig – comm tend annulus
                  in a CT capsule                                          Travels through trochlea (sup and med to eye)
               Intrafusal musc fibers are striated, but much              Inserts in the upper, post, and lateral quadrant
                  finer than extrafusal                                    Makes 54 degr angle to visual axis
               Extrafusal fibers form the bulk of the EOM                 When eye is turned 54 deg in, only SO elevates
               Musc spind = stetch receptor that receives            IO – oring in depression on orbital plate of maxilla
                  an efferent (gamma) motor innerv and an aff             post to the nasolacri orifice along the medial wall
                  (alpha) sensory innerv                              Inserts in the post, lat ,and lower quadrant of globe
               Retina provides a unique feedback on musc             54 deg angle to visual axis
                  movement not found in other skel musc                                     EOM actions
               Larger intrafusal fibers ontinue unmodified            1st                    2nd                  3rd
                  thoughout the spindoe, and lack neurl           SR Elev                     Incyclo              Add
                  contacts                                        IR   Depress                Excyclo              Add
               There are also discontinuous small intrafusal     SO Depress                  Incyclo              Abd
                  fibers                                          IO   Elev                   Excyclo              Abd
                                                                  LR Abd
                                                                  MR Add
                                                                        Epith – poor diffusion of gluc  must convert
    Cornea Hydration and Transparency – know p 91                        gluc glucose 1 phosphate  glycogen sotre
    and see class notes!!!!                                              in granules and lysosomes
   Corn has certain thickness and clearness                        Glucose utilization
   Needs tear film  smooth ant surf  uniform optics                O2 is needed to use glucose to provide energy to
   This balance is due to physiology of the layers, nutr, O2,           cells (corn epith, keratocytes, endoth)
    CO2, pH, metabolites                                              Normoxic conditions  full metabolism
   Impo topics:                                                          Glucose  gluc 6 phosphate  pyruvate 
     Bio chem. Of corn and pre-corn fluids                                   mito oxidized  much ATP
     Gluc meta by corn cells                                             This sequence is called the Embdem-
     Intact vs damages corn                                                  Myherhoff pathway
     Hydration prop of stroma                                            Needs at least 50 mmHg O2 (7%)
     Barrier prop of epith                                               Cell cytoplasm has pH of 7.3 in this reaction
     Fluid pump and barrier prop of endoth                               This is the usual meta in epith
     Physiological character of stroma                               Hypoxic metabolism – less O2 (but not anoxic!)
   Transparency                                                          Gluc gluc 6 phosph  pyruvate lactate
     Transmits > 90% of visible lt (400nm and up)                            + sm ATP
     Corn refracts lt                                                    This is called glycolysis
     N = 1.376                                                           Occurs when epith has little O2 (CL or
     Made of collagen and ground subst (stuff b/w coll)                     closed eyes)
        1.345 + 1.550 = 1.376                                             Occurs in endoth
     Stroma = 90% corn thickness                                   Lactate production and removal
         Made of coll type I                                         Hypoxic meta: pyruvate  lactate
         4-6% is proteoglycans (GAG)                                    dehydrogenase (LDH)  lactate (NOT lactic
         coll fibrils are small (20-40 nm diam w/ 60 nm                 acid!)
             space in b/w)                                            Lactate producion = pyruvate oxidase?
         coll fib are coated w/ GAG                                  Occurs in acidic pH (6.75) due to hypoxia 
         coll are organized into lamellae                               high CO2 amt (hypercapnia)
         original idea – coll in hexagon array                      In deep corneal tissue, never normoxic, so it’ll
             diffraction gradient                                        always have some lactate in cells (5-10 mM)
         later, we know that fibrils are spaced closely              If lactate > 10mM  hypertonic effect 
             together, but are just too small to scatter light           inflow of water  edema
         there is little coll order                                  In a healthy cornea, lactate is actively
         some order impo, but stroma clear b/c fibrils                  transported out of corn epith cells by lactate-H
             small and there is a balance b/w n of fibrils and n         xchg (both go OUT of cell), esp in acidic envi
             of ground subst.                                         Amt lactate transported  H gradient
         balance is due to hydtration of con tiss                    Then, most of lactate diffuses post to aq hum.
         chg in clearness due to:                                    If there is a prob w/ epith cells, some lactate also
              chg in fibril organization                                leak to tear film
              chg in n (of coll and/or grnd subst)                   Tear film lactate levels indicate corneal hypoxia
              chg in keratocyte light scattering properties          Buffering/CO2-bicarbonate
   biochem of corn and pre-corn fluids                               Buffering capacity = fluid’s capacity to respond
     interstitial fluid – w/in strorna                                  to pH change (higher buff capacity  less pH
     para-cellular fl – asso w/ cell layers b/w cells                   changes)  easier to stay w/in phys range
     pre-corn tear film                                              Phys range = 6.5-8.0
     aq humor                                                        PH and buffer in cornea = CO2/bicarbonate
     All these impo in hydration of cornea!                             levels (how they’re in equilibrium)
     O2 gradient                                                     CO2 + H2O carbonic acid  bicarbonate
         Open eye gets O2 from atmos b/c it dissolves in             CO2+ H2O  H2CO3  HCO3-
             tear film                                                Rxn is slow, but is catalyzed by CA (1st step)
         pO2 (mm Hg)– dissolved O2 meas w/ blood-gas                 CA is in cytoplasm and corneal cell membranes
             analyzer                                                 CA affects pH, CO2, and bicarbonate levels
         Open eye has steep gradient                                 Hernderson-Hasselbach eqn:
              tear film – 155 mmHg (21 % v/v)                        pH= pK(H2CO3) + log HCO3-__
              aq hum – 35-55 mmHg (5-7 % v/v)                                                 0.3*pCO2
     Glucose supply                                                  pK = measure of optimum pH where there’s a
         Need gluc for meta                                             inter-conversion of H2CO3 and HCO3-
         Bl secretes to  aq hum  endoth                           pCO2 = mmHg
             keratocytes  epith                                      HCO3 = mMoles/L
         Aq hum – 5mM gluc                                           CO2-bicarb-pH levels are fixed = if one changes
         Tear - <0.5 mM in healthy eye (elev in diab)                    all others change TOO
        People often overlook this fact in research and                     GAGs
         journal articles                                                  Anionic sites can be bound by H or other cations
    The following can also affect the bicarb-CO2 sys                      Ratios of bound cations to anions  change in
          Phosphate anions                                                 Donnan pressure
          carbonate anions                                               In living stroma, Donnan press = 40-60
          organic anions (like lactate, citrate, acetate)                  mOsm/L, which partly determines the capacity
    We need a balance b/w H and the anion buffers                          of stroma to absorb water.
    Bicarb-CO2-pH in open and closed eyes                            Sorbitol Pathway
    The H-H eqn helps us predict the bicarb-CO2-pH                       Stressed cells  alternate gluc meta
         relationship.                                                    Glucose  sorbitol dehydrogenase  sorbitol +
     Location          HCO3         pCO2            pH                      fructose (not lactate)
     Open Eye                                                             Sorbitol excess  osmotic effects and cell dmg
     Tears             5-25 mM      <5mm Hg         7.5-7.8               This is a prob in diabetes! (but not in normal tiss)
     Aq Humor          30 mM        55 mm Hg 7.4                 Normal vs Damaged Cornea
     Closed Eye                                                       Normal avg CCT = 0.535mm
     Tears             5 mM         55 mm Hg 6.95                     Normal range CCT = 0.45-0.60 mm
     Aq Humor          25 mM        55 mm Hg 7.1                      95% CO = 0.473-0.595 mm
    pCO2 in tears of closed eye = pCO2 in                            In periphery, corn is 23% thicker (avg 0.700 mm)
         lid/conjunctiva bl vessels (this is hypercapnia for          Dirunal Rhythim = cornea has cyclical changes in
         corneal epithelium                                              CCT throughout day
    stroma in eye also becomes acidic (7.1) in closed                Changes in hydrations  chg in thickness
         eyelids and under CL                                         Corn thickens overnite by 2-4%
 Gaseous physiology of corneal stroma                                Corn thins fast when awake
    Stroma has pH, pCO2, bicarbonate, and pO2                        Corn has a little lower than average around midday
         values b/w tear film and aq humor                            Diurnal cycle in CCT = +/- 2%
                                                                      CCT thicker in newborns (0.65 mm), but thins fast
 Location        HCO3 pCO2               pH        pO2
                                                                      Adult level achieved at 5-10 yrs old
                 (mM) (mm Hg)                      (mm Hg)
                                                                      For Caucasions, CCT no change w/ age 10-80 yrs
 Ant stroma 5-25            <5-55        6.95-     55-155
                                                                      CCT decreases w/ ate in Orientals
                                                                      CCT NEVER thickes w/ age!!!!
 Post stroma 25-35          45-55        7.1-      <55
                                                                      Diseased Cornea – very different!
                                                                  Disease             Result                  Reason
                                                               Collagen dis   Thinning =ectasia       Changes in
 Osmolality and Donnan Osmotic Pressure
                                                               (kerataconus) (70% of normal)          structure/mass of
   Organic anions (like lactate ) can have osmotic
                                                                                                      collagen lamellae
     effects on cells
                                                               Meta dis       Thickening              Perturbation of tissue
   This changes hydration of cells
                                                               (severe diab) (striae in post corn)    hydration
   What are other osmotic and oncotic effects?
   Corn fluids have certain concentration of                  Late stg       Much thickening         Hydration increase in
     dissolved molecules (inorganic cations and                corneal        over a few months       cornea
     anions)  det osmolality  osmotic effects on             dystrophies    (50% increase!) =
     tissue                                                    (Fuch’s)       decomnsensation
   If a tissue of freely permeable to the dissolved           Intraocular    Decompensation          Hydration due to corn
     molecules  no osmotic gradients                          surgery                                endo dmg
   If tissue has certain permeability  fl can be
     hypertonic (and remove water) or hypotonic (add               Corn Epith – maintains normal stromal hydration
     water) to tissue                                                Healthy cells keep normal thickness and clearness
   Any ionic concentration diff b/w cells or layers                 Epith = tite barrier  limits fluid in and out
      osm press                                                     Has passive barrier f(n) to stop hydration changes
   Tear film osmolality = 305 mOsm/L (high b/c                      Dmg to epith  dehydr or overhydr
     it’s likely to evap, esp when it’s unstable)                    Epith affects tear film stability
   Aq humor osmolality = 295 mOsm/L (b/c it’s in                        Unstable tear  evap more
     equilibrium w/ the bl vess of anterior segment                      Superficial cells of epith keep stable tear film
   Donnan osmotic (oncotic) press is different from                     Slight compromise of epith cells  disruption of
     above                                                                  tear film
   Donnan press relates to the ion binding in stroma                    If tear film is all removed by saline irrigation 
   Proteoglycans in corn stroma have a certain                             no tear film much evap
     concentration of (-) atoms  oncotic pressure (a                    Dry eye disease (KCS)  corn thin by 5%
     type of Donnan osmotic press)                                       Lack of tear film  corn thin by 15% (impo!)
   Some proteoglycans are:                                          Epith has a tite physiological barrier f(n)
      Mucopolysaacharids                                                Epith has limited permeability to water, cations,
      Glycosaminoglycans                                                   anions
            Epith high resistance ion-transporting cell layer            Lactate excess
             barrier                                                     Lower pH
         Healthy trans-epith electric potential difference               Higher CO2
             (PD) = 15-20 mV                                          Epith dmg vision prog = Sattler’s veil
         Corn has high electrical resistance                         Normal clinical setting – 15% max change CCT
         Limited ion permeability  PD                               But in REAL dmg to cornea:
         But there are net Na and Cl fluxes from stroma              Removal of epith  50% inc CCT w/in 3 hrs
             to tear-film across corn                                 Little further swelling happens after 3 hrs
         This Na/Cl flow may counter the permeability of             Gross epith dmg due to:
             inflowing cations or act as the basis of “fluid              Mechanical injury
             pumps”                                                       Corneal surgery
         Barrier and pumps can change in metabolic                       Epith dystrophies
             stress                                                   Gross endo dmg stromal edema CCT inc up
         Corn epith has risk of lacking glucose (esp when               to 200% or norm (=3X increase) (but not often)
             O2 is low), so O2 affects a lot.                         Endo dmg due to:
         Extended hypoxia and hypercapnia  pH
                                                                          Mechanical injury during intra-ocular
             decreases in cells
                                                                              surgery (cataracts)
         Glycolysis is inefficient in making ATP, so epith
                                                                          Endoth dystrophies
             cells use glycogen reserves under hypoxic
                                                                      In animal corneas:
                                                                                     Animal Corneas
         Glycogen  glucose-1-phophate  gluc-6-phos
         Hypoxia for too long  lose too much gluc             Animal    CCT (mm)        Similarity to humans
             gluc metabolism slows  too much lactate made       Rabbits   0.30-0.40       similar relative magn of chg to
             (via LDH) and too little ATPacidification                                   humans
             apoptosis (cell death) and slower mitosis (cell
             regen)increased desquamation (exfoliation) of      Cows       0.75-1.00     Relative chges are slightly
             superfic cellshurts barrier and electrical                                  smaller than for humans
             properties                                          Cats       CCT b/w rabbit and cow
         This desquamation is the driving force for XYZ         Monkeys    CCT b/w rabbit and cow
     Diurnal changes                                             Hydration and CCT
         Tear film pH changes in noctural hypoxia and                Stroma hydration increases w/ CCT linearly
             hypercapnia normal cycle of desquamation            Regional chg in thickness and hydration
         We see more desquamating cells on corneal                   Inc in CCT by stromal hydration corn swelling
             surface when wake up                                         posteriorly endo moves into ant chamb
         These desq cells are mixed w/ a few                         =posterior striae=middle of post corn surface is
             inflammatory cells  cesspool (overnite tear                 wrinkled
             film)                                                    when striae occur, inc in CCT is disproportionaly
     Epith barrier f(n)                                                  larger than changes in periphery thickness
         Epith barrier can be dmged by desiccation and               15% inc in CCT has 2% chg in periph = scleral
             cytotoxic chem. (b/c both affect PD/resistance)              clamping
         Desiccation = severe ocular surface disease like        Hydration (water contenct) of mammal’s stroma
             KCS or keratitis                                         Stroma has huge capacity to increase hydration
         Cytotoxic chem. = too much topical eye                      Hydr chges are never realized in situ (in living
             anesthetics                                                  eye)
         Increased evap  some disruption sof surface                Many lab experiments to see how much, but
             cells some desiccation (but ok amt)                         these methods must be physiologically relevant
         If dmg to eptih cells is largebarrier is hurt              Recent post-mortem (fresh) corn tiss from eye
             net fluid influx from tear film is too large                normal hydration of stroma
             can’t evaporate it allincrease corn hydration          Weigh tiss wet mass
   Thickness, hydration, and stroma                                  Dry and weigh dry mass
     Most changes in hydration are due to chges in stroma            Calculate water content
        b/c of the endo (some is by epith)                            W/ normal CCT hydration = 3.55 g water
     Thickness and hydration in dmged cornea                                                             g dry tissue
         Normal eye – CCT constant w/in 2% of avg                    this = corn tissue = 77%water
             (range 0.473-0.595mm)                                                      Water Content
         Mild dmg to epith  slightly thinning b/c of                      State              g water/g dry tiss       %
             more evap                                            Normal                             3.55               77
         Under much hypoxia and hypercapnia, CCT can             Slight Edema                        4.5               80
             increase 15% due to epith (and some stromal)         Substantial Edema                    6                83
             edema                                                Severe Edema (rare)                 10
         Cellular edema due to:                                  Max in lab eye                      75
      (never in living eye)                                                   Corn endo has fluid pump that removes water 
     Causes of gross hydration changes in isolated pieces                     corn thinning
          of stroma                                                        Pump counteracts a natural leak of fluid into
           Stroma piece w/o epith and endo can absorb a lot                   stroma (by imbibition press)
               of saline fast (5-15X) if immersed for a few hrs            If pump is hurt (by hypoxia or acid) stroma
           Absorbtion = imbibition                                            swells
           Smaller pieces (4X4 mm square) absorb more                     Leakage is purely passive
               than large ones (8X8, 12X12)                                Dehydr (deswelling or thinning) of isolated lab
           If leave in saline for 24 hrs 10X hydration                       cornea is dependent on extracellular [bicarb]
               increase                                                    Isolated sclero-corneal tiss in lab
           Hydration increases b/c of fluid imbibition due                    (sclera+endo+stroma…no epith) pumps fluid in
               to Donnan osmotic forces (measure of                            a stroma-to-aq direction vs an applied IOP
               cation/anion binding vs water binding of                    This shows a trans-ednothelial fluid pump
               proteoglycans in stroma)                                    Bicarbonate simulates pumpdeswelling
           Hydration can be blocked by polycations                        Endo fluid pump is bicarb and CO2 dependend
               (cetypyridinium chloride) chem precipitation               Pump transports bicarb from stroma to aq across
               of GAGs no water imbibition cornea is                         the apical membr of endo cells and into para-cell
               wafer thin in 24h saline                                        spaces
           This chem. precipitation changes the ground                    Water follows this bicarbonate
               subst chg in “n” balance b/c collagen and                  Limited data has been published indicating that
               GAGs opaque stroma                                             this pump can be inhibited by drugs that inhibit
     Swelling pressure of stroma                                              CA (all published lit uses unphysiological envi)
           Stroma imbibes (absorbs) water                                 This hypo seems good b/c it makes physical and
           We need measure imbibing (sucking) press                           # sense
           How much physical force is needed to stop                      Rate of corn thinning = 50um/h
               absorption?                                                 Net fluid pump rate = 5ul/h
           Swelling press = phys force (mm Hg) needed to                  5ul/hr/cm^2 pump thins stroma at 50um/h
               compress sdtroma and remove fluid                       Regulated barrier hypo
                  Hydration and Swelling Press                             fixes problems w/ 1st hypo
                   Stroma Hydration             Swelling Press             endo is not a tite barrier like epith
                   (mg water/mg dry tiss)       (mm Hg)                    endo does have finite permeability to cations and
Easy                             8                       4                     anions
½ hydr                           4                      40                 major role of endo is NOT just a passive barrier
harder                                                                        (w/ pump vs leakage)
Dessicated                       3                     150                 permeability of endo barrier is regulated by cell
(dry) stroma                                                                   metabolism and cell volume
Normal eye                                            40-60                water will leak into stroma unless it’s actively
                                                                               kept out by changes in permeability of endo to
      Hydration changes in sclera-supported stroma                            water.
          More swelling in center than peripheral stroma                  Cell volume chg  para-cell space path
          Scleral rim less fluid imbibition in periphery                     chgchanges the net ionic permeability and
                 Stroma and Scleral Hydration                                  fluid flow across cell layer
                                                                           In lab, brief exposure to lactate chg cell
Sample                   Soln                    Increase in
                                                                               shapechg para-cell space
                                                    24 hrs
                                                                           This theory no excludes the existence of a pump,
Stroma + scleral rim     Saline                     3-4X
                                                                               but proposes that controlled changes in pH, CO2,
                         Bicarb-CO2-glucose          2.5X
                                                                               and cation in stroma (mediated by changes in
                         (like aq humor)
                                                                               endo permeability) determines the stromal
Mount stroma and         Saline                       3X                       hydration (in part by Donnan osmotic equil
sclera and apply         Bicarb-CO2-glucose           2X                       that’ll be established under different pH, CO2,
hydrost press to post –                                                        and cation levels)
like IOP
                                                                     Corneal stroma is influenced by corn metabolism chges
                                                                       In past, stroma was considered inert and a passive
            Increase in wet mass is inversely related to                 responder to changes in epith or endo cell f(n)s
             hydrost press                                             This ignored keratocytes and gave no explanation of
         Net tendency of stroma to imbibe fluid shows the                how ion concentrations in stroma (for Donnan eq) are
             balance b/w:                                                 controlled
              (applied pressure) – (imbibition press)                  Today, we believe in living corneal stroma
         Imbib press = physical tendency to imbib water               Newer ideas show faults in pump theory
   Role of Endo in maintaining normal stromal hydration               If pump-leak is only basis of stroma hydration, then
     Controversial! (most texts say pump-leak hypoth)                    CO2 levels would be impo for bicarb levels for pump
     Pump Leak Hypo                                                   In old theory, high bicarb and CO2better pump
     But normal fluxes of CO2 and bicarb are from the              CN III nucleus (in midbrn) has paired subnuclei for each
      aqueousstromatear film                                       musc except:
     When lids closedecreases fluxcornea thickens!                 Levator – 1 central caudate sub-nucleus for 2 levators
      (should thin!)                                                  Autonomic nucleus (EW nucl) – single, but divides
     Labs show that pump is not totally bicarb-dependent,                into 2 horns at anterior end to 2 eyes
      and can work w/o extracell bicarb                               There are a few scattered large multipolar cells on the
     Other labs show that corn thinning can occur when                   midline raphe b/w right and left oculomotor masses
      no net fluid pump is measured (when endo layer is                   that innervate SR instead of MR
      intact)                                                       CN III nerve fibers
     Pump hypoth doesn’t take into account the fact that             CN III contains 3 types of nerve fibers
      stroma pH changes under hypoxia-hypercapnia                          Motor – bulk
     Labs no show that the pump is changed in hypoxia                     Sensory – 10%, proprioception from musc
      (although hydration and stromal swelling and                             spindles
      deswelling is very bicarb-pH dependent)                                   Most of these sensory neurons have somata
     Therefore, it is proposed that changes in stroma                              in brainstem, NOT the trigeminal gang.
      bicarb/pH are by endo controlling stroma bicarb                      Autonomic – parasym
      concentrations, pH levels, and ambient CO2 levels.              There is 1 nerve fiber for 3 musc fibers (this is a very
     Best argument vs pump hypo is clinical                              high ratio in body)
       According to pump, bicarb and CAbetter                       Motor nerve to IO gives rise to the short motor root
           pump                                                            This root has thinly mye pregang parasym fibers.
       CA inhibitors should make pump worse and                           It synapses in the ciliary gang
           cause edema…BUT                                                 Postgang parasym fibers to eye are also mye
       Putting CA inhibitors in eye does NOT change                       Pregang < postgang diffuse system
           corn thickness at all (increase or decrease)             Ciliary ganglion = postgang parasymp cell bodies
       CCT is unaffected by inhibitors of cell                       It is located b/w LR and optic N
           bicarbonate                                                It receives 3 types of nerves:
       Systemic CA inhibitors (like acetazolamide)                        Pregang parasymp motor root
           don’t cause edema (and actually reduces it)                          Neurons are in midbrn
       Topical CA inhibitors (dorzolamide) no causes                           Synapse in cil gang w/ postgang N
           much corneal oedema
                                                                                97% innervate ciliary musc-->accom
                                                                                also activate sphincter musc-->pupil const
CN III – Oculomotor N – p 15, 162, 165                                          inhib dilator musc
   CN II – VIII supply eye (CN II = optic n)                              Postgang symp motor root – no synapse
   Supplies 8 musc:                                                            Some texts say there’s a separate symp root
     EOM (skel, motor)                                                             that goes through cil gang, but none found!
          MR                                                                   Some travel w/ nasocil root of CN V-1
          SR                                                                       through cil gang
          IR                                                                   Constricts dilatordilate
          IO
                                                                                Inhib sphincter m
          Levator Palp Sup (LPS
                                                                                Inhib ciliary m maybe?
     All 4 intrinsic musc of eye (smooth, parasym)
                                                                           Sensory root (no synapse) – there are 2 proposed
          Iris Sphincter musc - excite
                                                                               routes from CN V
          Iris dilator musc - inhibit
          Ciliary musc - excite                                                Nasocil root (from CN V-1) – innerv
     NOT LR and SO                                                                  Cornea
   CN III divides into 2 parts  enters orbit via Sup Orbital                       iris root
    Fiss (SOF) both parts pass through Ann of Zinn                                  fissure around apex of filtration angle
   Superior division (smaller) supplies:                                       Orbitociliary root (from CNV-2)
     SR                                                                             Enters eye via IOF to cil gang
     LPS                                                                            Somatosensory fibers of CN V origin
   Inferior division supplies:                                                      May not be present in some eyes, but if
     MR                                                                                 so, maxillary fibers reach eye via
     IR                                                                                 rami ocularis
     IO                                                                        Rami orbitales from CN VII may also pass
     Sphincter                                                                     through cil gang
     Dilator                                                         After cil gang, nerves enter eye as short cil nerves
     Ciliary muscle                                                       Not every short cil nerves have all the fiber types
   All indiv branches enter musc on ocular side except:                   8-12 short cil nerves from cil gang reach eye
     IO – enters posterior side                                               close to optic nerve in a circle
     Levator – enters peripheral side                                     short cil nerve + short post cil art = circle of Zinn
                                                                           after they leave cil gang, they branch out before
                                                                               reaching the eye
                                                                              posterior cranial fossa (w/in subarachnoid
                                                                                space) middle cranial fossa 
     Ganglion of “Axenfeld”                                                    sup orbital fissureorbit
          Its accessory to cil gang, but not in all people            As CN IV passes forward in the lateral wall of
          Can take over cil gang f(n)s if dmged                           cavernous sinus, it is below CN III and above
     There are also ectopic neurons in eye that aren’t in cil             CN V-1 (ophthalmic nerve)
         gang.                                                         As it nears the anterior end of the sinus, it crosses
   When you accommodate, 3 things happen:                                 over CN III
     Accom – by cil musc                                              It enters orbit via SOF outside of Annulus of Zinn
     Converge – by MR                                                 It passes beneath periorbita and above LPS and SR
     Pupil constr – by sphincter                                      It then fans out into 3-4 branches and enters SO on its
   Paralysis of CN III – 5 types                                          external surface near the lateral border.
     Ptosis – droopy lid b/c levator musc paralyzed                 CN IV contains
          Tarsal musc still works, so eye no close all the            Somatic motor fibers – medullated as the
              way                                                          corresponding fibers in CN III
     Squint involving:                                                Sensory – proprioceptive fibers
          Depression (SO)                                           CN IV paralysis (of SO)
          Abduction – divergence (LR & SO)                            Vertical squint
          Intortion – incyclorotation (SO)                            Can’t look down when eye is adducted b/c SO is the
          This all occurs b/c SO and LR are the only                      only depressor in adducted position
              EOMs still working                                       Head’ll be tilted down and twds unaffected eye to
     Fixed semi-dilated pupil                                             avoid diplopia
          Occurs from unopposed action of symp N.S.                   Affected eye rotates mediallydiplopia when
          There’s no pupil constr to lite                                 looking down
          There’s no near reflex miosis                            CN V – Trigeminal N (p 168 pic)
     Slight exophthalmus (sometimes)=eye protrudes out              Largest CN
          CN III keeps EOMS toned. When CN III                      Has 2 roots:
              dmges, EOMS relax and eye sticks out                     Sensory – larger root
     Lose accomodation                                                     Goes to face, scalp, mouth, teeth, nasal cavity
   If the pathway to cil gang is destroyed, papillary reflex for           V-1 contains a few proprioceptive fibers of
    accom will persist, but direct reflex to lite’ll be lost                    EOMS (b/c most EOM fibers go w/ CN III)
   This is b/c the postgang parasymp fibers from cil gang                  V-3 Contains proprioceptive fibers of chewing
    only act for the lite reflex                                                muscles
   The near reflex miosis follows a different pathway                 Motor – smaller root for chewing musc
   Small pupil = miosis                                             CN V emerges from ventral pons.
   Lg pupil = mydriasis                                             Fibers that make sensory root orig from unipolar cells in
   Sensory fibers travel w/ CN III all the way to CNS…they           trigeminal ganglion
    do NOT go to trigeminal gang                                     Ganglion lies in the middle cranial fossa = depression of
CN IV – Trochlear N                                                   the bone near the apex of the petrous part of the temporal
   Smallest CN                                                       bone
   Has 3500 fibers                                                  There are 4 trigeminal nuclei
   Innerv SO on orbital side (all other EOM are innerv on             Ponsdorso-medial course twds principal sensory
    bulbar side)                                                           nucl
   Its nucleus is in the floor of cerebral aqueduct in midbrn,        Before reaching primary sensory nucl:
    oppo of inferior colliculus, and receives afferent info                 50% divide into asc and desc branches
    from:                                                                   50% ascend or descend w/o division
     Rostral interstitial nucleus of the Medial Longitudinal          desc fibers end at level of C2 and synapse w/ cells
         Fasciculus (MLF) and interstitial nucl of Cajal, which            making up the nucleus of the spinal trigeminal tract
         mediate vertical and torsional control of gaze                     the nucl of spinal trigeminal tract divides into 3
     Frontal eye fields, sup colliculus, dentate nucl, and                     areas for:
         other cortical areas via the nucl of the post                           CN V-1 ophthalmic tract
         commissure MLF                                                          CN V-2 maxillary tract
     Direct input from sup coll                                                 CN V-3 mandibular tract
     Nucleus prepositus hypoglossi                                         The nucl of sp trigeminal tract also divides into 2
   CN IV course:                                                               f(n)al levels:
     Has a long and unique intracranial course                                  Touch
     Only CN that                                                               Pain and temp
          decussates completely                                       Asc fibers go to mesencephalic nucl in midbrain
          emerges on dorsal side of CNS                                    Asc fibers are large and mye
                                                                            Mesencephalic nucl is made of a column of
                                                                                unipolar cells
            Peripheral branches of neurons get proprio                              These symp fibers innerv dilator of iris,
             signals from chewing musc, face musc, teeth,                             but other symp fibers may reach dilator
             and EOM, and give signals to mesencephalic                               via other routes, like bl vessel walls
             nucl                                                      CN V-2 – maxillary Nlower lid and conj, little to
         These neurons are the only primary neurons in                 eye
             the body located in CNS                                     Intermed size division
     Motor nucl is ovoid and made of large multipolar                   Has only sensory fibers
        nerve cells                                                      Some postgang fibers may join it
   There are 3 divisions:                                               Passes through foramun rotundam and becomes
     CN V-1 – ophthalmic Nnose tip, upper nose,                           infra-orbital nerve
        forehead, upper lid and conj                                     Has 6 branches:
         Smallest division                                                  Middle meningeal n – branch before
         All sensory w/ a little symp ANS motor                                 foramon rotundum
         Runs fwd in lateral wall of cavernous sinus                             sensory to dura mater around the
             enclosed in its own sheath of dura. (CN III and                          anterior half of the middle cranial fossa
             IV pass above it)                                               Sphenopalatine ganglion branches (2)
         Cav sinusSOForbit  divides into 3 nerves                             Connects CN V-2 w/ pterygopalatine
              Lacrimal N                                                             ganglions
                   Smallest branch                                               Contain autonomic fibers from facial N
                   Goes into orbit outside annulus of Zinn                           to lacrimal gland
                   Travels through lacrimal gland, but                      Sup, post, middle, and ant alveolar (dental) n
                       DOES NOT innerv it at all!                                 Supplies maxillary sinus, upper teeth,
                   Innerv upper lid, upper conj, part of                             cheek
                       forehead and temples                                  Orbitociliary n. to cil gang
              Frontal N                                                          Not always present
                   Largest branch                                                Maxillary sensory rootIOFrami
                   Goes into orbit outside annulus of Zinn                           ocularisorbitcil gang
                   Near front of the orbit, it divides into 2               Zygomatic nerve
                       nerves:                                                    Innerv skin over the anterior part of the
                        Supratrochlear N – forehead skin,                            temporal region up to the lateral orbital
                           upper lid, upper conj                                      margin and skin over zygo bone (cheek)
                        Supraorbital N (lger)– forehead,                         After infraorbital n passes via IOF, zygo
                           part of scalp, upper lid, upper conj                       nerve branches off
                        These 2 have overlapping fields                          Has 2 branches that enter zygomatic
              Nasociliary N – has 5 subbranches                                      canal in the zybo bone and emerge on
                   First branch off CN V-1                                           facial side of bone to innerv skin nearby
                   Passes inside annulus of Zinn                                      Zygomaticaofacial N
                   Has 3 branches to eyeball that supply                              Zygomaticotemperoal N
                       mainly cornea, w/ some to sclera, cil                      Old theory – gives a communicating br
                       body, and iris root                                            w/ ANSlacr Nlacr gland…NOT
                        2 long cil N                                                 TRUE
                        nasociliary sensory root to cil gang                Infra-orbital n
                        these travel through choroids (but                       Divides into many sm branches to skin
                           don’t innerv choroid) and give 20%                         of upper lip, mucous of upper gum,
                           unmye baroreceptor fibers to                               lateral and lower nose, and skin and
                           angular recessgive sensory IOP                            conj of lower lid
                           info to brain                               CN V-3 – Mandibular Njaw to preauricular area
                   has 2 branches that no go to eye                     Largest division
                        Anterior ethmoidal branch – innerv              Goes through foraman ovale
                           mucous membrane of nose skin                  Innerv lower teeth, gums, skin in jaw, lower lip,
                        Posterior ethmoidal branch – innerv                part of auricle, lower face, chewing musc,
                           ethmoidal and sphenoidal sinuses                 mucous membr of tongue and floor of mouth
                        Infratrochlear N (terminal branch)              It may contain proprioreceptor fibers and
                           – supplies skin and conj around                  somatosensory fibers
                           medial canthus, root of nose,                 Carries motor fibers to chewing musc
                           lacrimal sac, canaliculi, and               Herpes simplex is the most comm dis to CN V
                           caruncle                               CN VI – Abducens N
                   From the internal carotid plexus, post-          Most vulnerable CN b/c it can be affected by all lesions
                       gang symp ANS anastomose w/ nasocil            nearby or far away
                       N and travel in long cil nerves to
                                                                     Has 6600 nerve fibers to LR
                                                                     CN VI nucleus:
     Small nucl @floor of 4th ventricle close to median           deep surface of facial musc (these branches are divided
      plane                                                       into temporal-facial and cervico-facial divisions.)
     Has lg and small multipolar nerve cells                    Motor root innerv:
     Receives afferent input from:                                Musc of facial expression
       Corticonuclear tract                                       Orbicularis oculi
       MLF                                                      Sensory root innerv:
       Tectobulbar tract                                          Taste
       Paramedian pontine reticular formation (PPRF)              Pregang parasymp fibers to parotid, submand,
       Nucleus prepositus hypoglossi                                  subling salivary glands and lacrimal gland (none to
       Contralateral medullary reticular formation                    eyeball)
     CN VI course                                               Pregang parasymp fibers go from facial n @ geniculate
       CN VIcav sinusSOFannulus of Zinn                       ganglionbecomes greater petrosal ndeep petrosal n
           orbitdivides into 3-4 branchesLR on                 (symp fibers from internal carotid plexus) joins greater
           internal side facing eyeball                           petrosal n combo becomes nerve of pterygoid canal 
     CN VI contains (like CN IV)                                 pterygopalatine gang where parasymp synapse
       Somatic motor fibers                                     Parasymp innerv of lacrimal gl (see p 39)
       Sensory-proprioceptive fibers                              Old path: has anastomosing branch from zygomatic
     CN VI paralysis (of LR)                                          N to lacrimal N
       Can’t abduct eye beyond primary gaze                            Doesn’t exist!
       Diplopia on looking in direction of affected side               Lacr n has no parasymp fibers!
     Fractures @ base of skull can hurt CN VI.                    Correct path: based on sci basis
     It has a long intracranial course, so can be hurt in              Postgang parasym (and symp): come from
      many places                                                           pterygopalatine gangbecome rami
     Esp vulnerable @ sharp apex of petrous temporal                       orbitalesenter IOF divide into 3 routes
      bone b/c it makes a sharp bend                                         Rami lacrimales – go directly to lacr gl
     Increased IOP can hurt it b/c brainstem is pushed                      Rami ocularis – go directly to eyeball
      caudally twds foramen magnum and stretches nerve
                                                                             Enter IOF go posterior out via SOF mix
     These can also hurt CN VI:
                                                                                 w/ other ANS in retro orbital plexus
       Microvascular infarcts
                                                                                 return to orbit via SOFinnerv eye, lacr gl,
       Vascular compression
                                                                                 and orbital bl vess
       Tumoral compression
                                                                 Paralysis of CN VII
       Direct trauma
                                                                   asymm face
       Infection
                                                                   no tears
Neural control of eye movements                                    no saliva
   Horizontal conjugate eye movements:                            no taste
     Saccades                                                ANS periph N to orbit and eye:
     Smooth pursuit
                                                                 symp
     Vestibulo-ocular reflex (VOR)
                                                                   innerv is ipsilateral!
     Optokinetic reflex
                                                                   Long pregang distance = hurt easilyHorner’s
     All the above share final common path via abducens
                                                                     Syndromedroopy eye
                                                                   lat horn in thoracic sp cord (pregang cells) white
   PPRF – premotor control for horiz gaze movements and
                                                                     ramusshort distance sup cerv gang (synapse,
    controls eye velocity by sending:
                                                                     postgang cells)  int carotid artery plexuslong
     excitatory interneurons to ipsilateral abducens nucl           distanceeye/orbit
     inhibitory neurons to contralat abduscens nucl
                                                                   (sweat glands innerv by 1 synapse @ gang)
   Vestibular nucl and the per-hypoglossal complex also           orbital distr (4)
    project to abducens nuclei and mediate the VOR and                lacr gland
    smooth pursuit respectively
                                                                           symp controls bl vess of lacr gland
   w/in abducens nucl, there are:
                                                                           if symp hurt, still secrete ok
     motor neurons that innerv ipsi LR
                                                                           mainly para innerv to secrete
     internuclear neurons to contralat MR subunit of
                                                                      sup/inf tarsal muscles
         oculomotor nucl via MLF
                                                                           in lids
     this gives yoked horiz eye movements
                                                                           dual innerv
   lesion in MLFslow or no movement of adducting eye
    jerky eye movements and nystagmus of abducting eye                         symp – excite
                                                                               para – inhib
CN VII – Facial N
                                                                           works w/ levator to keep lids open…lose
   Has motor and sensory parts (nervous intermedius)
                                                                              sympdroopy lid
   Emerges from brn stem at lower ponsinternal acoustic
                                                                           more sympwide eye in fight/flight
    meatusfacial canal in petrous portion of temporal bone
                                                                      orbital musc of muller – retracts eyeball
    transverses parotid glanddivides into many branches
                                                                           remnant from animal life
                                                                           symp-excite
         orbital bl vessels                                       (first 3 = intrinsic sm musc of eye)
     ocular distr (5)                                           para arrives via 2 diff routes
         dilator m - excite                                       short cil N – CN III
         sphincter m - inhib                                      rami oculars – CN VII
         ciliary m?                                        Sensory N to eye and orbit
            drugs/physiology see effects of symp inhib        all sensory n from CN V gang (unipolar sensory
            anatomy no see innerv                              neuronsaxons to target….no synapse)
            controls accom, no need symp                    ex. CorneadendriteCN V gangaxonbrain
               innerv…interacts w/ brain                     some connect to multipol motor neurons in sp
            so cil m prob just PARASYMP innerv                 cordventral rootskel musc reflexsensory organ
         ocular bl vess (arteries)                             sense contractionbrainadjust musc
            if eye bl vess innerv, they dually innerv       to eye, most are from nasocil br of CN V-1
            bl vess w/o innerv = iris, retina               some sensory goes via CN V-2 (maxillary)foramen
            bl vess w/ innerv = choroid, cil body,             rotunduminfraorbita njoins rami fibersorbitocil N
               trabeculum (very little..insign)                 cil gang orbitocil root
            capill never innerv                             branches of CN V-1 (opthal br)
         trabeculum?                                            frontal n.
     Symp fibers may enter eye via these routes (4):            lacrimal n
         Short cil N                                            nasocil n = 3 br give sensory to eye!
         Long cil N                                                  Nasocil sensory root to cil gang (main sensory)
         Bl vess                                                         No syn in cil gang
         Rami oculars (w/ CN VII)                                    2 long cil nerves – near 3, 9:00 equator, white
   Parasymp NS                                                           (short cil nerves – near post pole)
     Has 2 srces for the eye                                         symp fibers join sens nerveseye
         CN III                                             ocular distr
            CN III nucl in midbrain (auton nucl=EW              cornea
               nucl)long distancecil gang, accessory                most sens fibers go to cornea
               gang of Axenfelt, and ectopic cellsshort              forms 2 plexi (both detect same stimulus)
               cil Neye                                                  epith
            Short cil n insert near post pole, circle of                 ant stroma
               Zinn, or in dura of Opt N                         sclera
            Gang of Axenfelt is a back-up to cil gang                most sens fibers to sclera go to ant episclera
               and is not in every indiv                         uvea
            In midbrn path for near meiosis no = path                cil body – 20% of unmye fibers in cil body ant
               for light meiosis                                         stroma are sensory
         CN VII                                                          @ root, may be baroreceptors to detect IOP
            CN VII nucl in ponslong                                         and tell brain
               distancepterygopalatine gangrami                         no sensory innerv to cil musc
               ocularis (short dist)eye                              iris – sensory not always present
            Some rami may pass through cil gang                          if present, @ root
     Orbital distr (3)                                               choroids – no sensory innerv
         Lacr gl – CN VII – main control of secretion                    sensory nerves in choroids are just passing
            If lose para innervno tears secrete                             through
         Bl vess – CN VII – dual innerv                         trabeculum (?)
            Only in bl vess that have any innerv                     has sensory fibers, but so fewinsign
         Tarsal musc – CN VII – inhibitory                 Also know:
     Ocular distr (5)                                           orbit – p 10-17
         Cil M – CN III – excitatory                            orbital art/venous flow-p 157-162
         Spincter M – CN III – excite                           cell junctions
         Dilator M – CN III – inhibit                           pictures on test!!!!!
         Bl vess – CN VII
         Trabeculum? – CN VII

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