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The canine eye lens depression and


                  The canine eye: lens depression and
                           aqueous outflow
                                                  E. Michael Van Buskirk

          The effects on facility of outflow of lens depression (controlled mechanical retrodisplaceinent of
          the crystalline lens to simulate cyclotonia in excised eye preparations), prolonged perfusion,
          and intracameral hyaluronidase were evaluated in 16 pairs offreshly excised canine eyes. Lens
          depression increased facility of aqueous outflow by an amount greater than could he attributed
          to mechanical or temporal disruption of the hyaluronidase-sensitive outflow barrier and ap-
          pears to act, at least in part, on the hyaluronidase-resistant portion of the outflow barrier.
          These data suggest that in addition to accelerating the washout effect, mechanical tension on
          the iridocorneal angle in the dog increases facility of aqueous outflow in a manner similar to the
          direct trabecular component of cyclotonic-induced facility increases observed in primate eyes.

                        Key words: canine eye, facility of outflow, cyclotonia, lens depression,
                                     "washout", hyaluronidase-sensitive barrier

    I revious segments of these studies have                          effects may be paradoxical and, if exploited,
    described characteristic features of the ca-                      may provide insight into common mecha-
    nine aqueous outflow system, many of which                        nisms for aqueous outflow shared by the
    have contrasted the canine with the primate                       spectrum of mammalian species.
    eye. 1 " 3 Both mammalian groups, however,                           Parasympathomimetic agents increase fa-
    appear to share some features, including an                       cility of outflow in primates by means of
    ocular hypotensive effect from pilocarpine                        ciliary muscle contraction against trabecular
    administration to glaucomatous eyes. 4 " 6 At                     meshwork, in part, through scleral spur.7
    first glance, a common pharmacologic effect                       The experimental technique of lens depres-
    between two mammalian species appears in-                         sion simulates this effect by mechanically
    tuitively predictable. On the other hand,                         pulling on the ciliary body through the lens
    considering the numerous differences be-                          zonules. Although force vectors of lens de-
    tween the two outflow systems, these similar                      pression are more centripetally oriented than
                                                                      those of true ciliary muscle contraction, their
                                                                      combined effect is sufficiently comparable to
                                                                      increase, reversibly and reproducibly, facil-
    From the Division of Ophthalmology, Department of                 ity of aqueous outflow in excised primate
      Surgery, The Milton S. Hershey Medical Center, The
                                                                      eyes.8"10 The present study applies this
      Pennsylvania State University College of Medicine,
      Hershey.                                                        technique to enucleated canine eyes, recog-
    This study was supported by NIH Research grant                    nizing that changes in facility which may be
      EYO1563 and Research Career Development Award                   quantitatively comparable to those observed
      EYO0051 from the National Eye Institute.                        in the primate need to be assessed in the
    Submitted for publication April 16, 1979.
                                                                      light of known anatomic and physiologic
    Reprint requests: E. M. Van Buskirk, M.D., Depart-
      ment of Ophthalmology, University of Oregon Health               differences among the separate mammalian
      Sciences Center, Portland, Ore. 97201.                          species.

    0146-0404/80/070789+04$00.40/0 © 1980 Assoc. for Res. in Vis. and Ophthal., Inc.                             789
                                                                                                              Invest. Ophthalmol. Vis. Sci.
    790     Van Buskirk                                                                                                          July 1980

                                                                                   terior chambers of six pairs of eyes were irrigated
                                                                                   with 10 ml of Hanks' solution containing 300 U/ml
                                                                                   bovine testicular hyaluronidase (Wydase; Wyeth
                                                                                   Laboratories, Philadelphia, Pa.). This solution was
                                                                                   allowed to remain in the anterior chamber, with
            a. 2.0                                                                 the corneal fitting removed, at ambient pressure
            5                                                                      for 30 min and was then removed by irrigation
           £ 1.6                                                                   with 10 ml of Hanks' solution. Because of the non-
                                                                                   specificity of bovine testicular hyaluronidase for
                                                                                   canine anterior chamber angle mucopolysac-
            = 1.2                                                                  charides, the relatively high dosage of hyaluroni-
                                                                                   dase was chosen on the basis of previously re-
                 0.8                                                               ported data to ensure as complete a dissolution of
                                                                                   the hyaluronidase-sensitive barrier to aqueous
                              NO HYALURONIDASE • — • — • WITHOUT LENS DEPRESSION   outflow as possible.1" 2
                 0.4          NO HYALURONIDASE O     - O WITH LENS DEPRESSION

                              IC. HYALURONIDASE A    A WITHOUT LENS DEPRESSION
                              IC. HYALURONIDASE A    A WIIH LENS DEPRESSION
                TIME (minutes) 60         120        180                              For the eyes not treated with hyaluroni-
    LENS DEPRESSION (units)     2            4          6                          dase, mean baseline facility of outflow was
    Fig. 1. Effects of prolonged perfusion and lens                                0.39 ± 0.03 /Ltl/min/mm Hg* for both the 10
    depression on facility of outflow in 16 pairs of                               eyes to be subjected to lens depression and
    canine eyes, of which six pairs had been treated                               the 10 fellow control eyes. After 6 U of lens
    with intracameral hyaluronidase.                                               depression, mean facility of outflow increased
                                                                                   to 1.43 ± 0.08 /Ltl/min/mm Hg for an average
    Methods                                                                        total increase of 275% ± 102 or an average
        Facility of aqueous outflow was estimated in 16                            facility increase of 96% ± 40 per hour. In the
    pairs of anatomically normal eyes, excised within 3                            fellow, control eyes perfused over the same
    hr postmortem from mongrel dogs, by quantita-                                  length of time, mean facility increased by an
    tive aqueous perfusion at room temperature with                                average total of 163% ± 25 or 54% ± 8 per
    Hanks' balanced salt solution at an intraocular                                hour to a mean of 1.00 ± 0.23 /Ltl/min/mm
    pressure of 20 mm Hg. The eyes were stored and                                 Hg. The mean rate of facility increase per
    prepared for perfusion as previously described.'                               hour was significantly higher in the eyes sub-
    Following removal of a 5 mm button from the cen-                               jected to lens depression than in the control
    tral cornea, a radial iridotomy provided communi-
                                                                                   eyes (0.01 < p < 0.02) (Fig. 1).
    cation between the anterior and posterior cham-
    bers. The lens was carefully inspected to ensure an                               Of the six pairs of eyes which were pre-
    intact anterior capsule. The anterior chamber was                              treated with hyaluronidase, initially mea-
    perfused by means of an acrylic 5 mm corneal                                   sured facility of outflow averaged 1.06 ± 0.06
    fitting described by Grant." The lens depression                               /Ltl/min/mm Hg for those to be subjected to
    apparatus was fitted to one member of each pair.                               lens depression and 1.33 ± 0.63 for the con-
    As before, the facility of outflow estimated from                              trol eyes pretreated with hyaluronidase but
    the flow measured after 1 hr was arbitrarily desig-                            not subjected to lens depression eyes. Facil-
    nated "baseline facility of outflow" to permit ade-                            ity increased with lens depression to 1.61 ±
    quate time for viscoelastic equilibration.1 The
                                                                                   0.16 /Ltl/min/mm Hg for an average total in-
    plunger of the lens depression apparatus was ad-
                                                                                   crease of 58% ± 35 or 19.33% ± 11 per hour
    vanced from the faceplate of the corneal fitting a
    distance of 2 U (1.1 mm) every hour to a maximum                               (Fig. 1). There was no significant difference
     of 6 U over 3 hr of additional perfusion; the fellow,                         between measured facility of outflow with
     control eye was continuously perfused for 4 hr                                 0 U and 2 U of lens depression (0.1 <
     without lens depression. The plunger was approx-                              p < 0.2), but the facilities measured at 0 U
     imately in apposition with the anterior surface of                             and 6 U of lens depression were significantly
     the lens with advancement of 2 U.
        Before insertion of the corneal fitting, the an-                           * All means are expressed ± S.E.M.
    Volume 19
    Number 1                                      Canine eye: lens depression, aqueous outflow 791

    different (0.01 < p < 0.02). Over the same          the values for posthyaluronidase facility were
    length of time, facility of the control eyes in-    variable. It is likely that transtrabecular driv-
    creased from 1.33 ± 0.63 /ul/min/mm Hg to           ing pressure facilitates the action of in-
    1.46 ± 0.53, for an average total increase of       tracameral hyaluronidase by delivering the
    16.7% ± 25.0 or 5.5% ±8.1 per hour.                 enzyme to its site of action deep in the irido-
    These initial and final facilities were not sig-    corneal angle and by washing downstream
    nificantly different (0.6 < p < 0.7).               residual mucopolysaccharide by-products.
       In spite of pretreatment with a high dose of     Since the experimental procedure of lens de-
    intracameral hyaluronidase, some time-de-           pression necessitates increased anterior seg-
    pendent facility increase persisted without         ment manipulation, undoubtedly the proce-
    lens depression in two eyes by as much as           dure itself contributes a kind of washout
     18%/hr whereas it was under 3%/hr in the           effect by partially disrupting the hyaluroni-
    remaining 4 eyes. Among the hyaluronidase-          dase-sensitive portion of the outflow barrier.
    treated eyes which were subjected to lens           This effect cannot be clearly separated, by
    depression, the facility increase exceeded           the techniques employed in these studies,
    20%/hr in four of six eyes, but the differences      from any direct action of lens depression on
    between the mean hourly facility increase            the nonmucopolysaccharide elements of the
     with and without lens depression were               filtration meshwork. However, lens depres-
     not quite statistically significant (0.05 <         sion did increase facility in most of the eye
     p<0.1).                                             studies by more than could clearly be attri-
                                                         buted to washout alone. Moreover, lens de-
    Discussion                                           pression continued to increase facility in the
        Although mean baseline facility of outflow       hyaluronidase-treated eyes in which the
    in these canine eyes was comparable to that          hyaluronidase-sensitive component of the
    observed previously, it was somewhat high-           outflow barrier had been previously elimi-
    er. ' Because of the mechanical fragility of the     nated or markedly diminished. Although lens
    hyaluronidase-sensitive component of the             depression-induced dissolution of iridocor-
    canine aqueous outflow barrier, the higher           neal angle mucopolysaccharides probably ac-
    facilities which were observed in these eyes         counted for a portion of the facility increases
    may have been attributable to the greater             observed, the remaining portion may well
    manipulation necessitated by the corneal              have resulted from direct action on the re-
    trephination and radial iridotomy. On the             sidual hyaluronidase-resistant portion of the
    other hand, initially measured posthyaluron-          canine outflow barrier. It is this latter effect
    idase facility tended to be lower in this study       which may be relevant to outflow modulation
     than previously observed, an effect also at-         in the primate.
     tributable to the change in technique. Al-              Increases in facility of outflow induced by
     though this difference may simply reflect the        cyclotonia in living, or by lens depression in
     relatively small number of eyes studied, the         excised, primate eyes may be partially but
     lack of transtrabecular aqueous flow at the          not entirely attributable to separation of the
     ambient intraocular pressure extant during           opposing walls of Schlemm's canal and resul-
     enzyme exposure undoubtedly was a major              tant partial intracanalicular circumferential
     factor. A large volume of hyaluronidase, em-         flow.8- 12~13 Schlemm's canal canalicular wall
     ployed in an attempt to compensate for the           separation is anatomically precluded in the
     lack of transtrabecular driving pressure, suc-       dog by the absence of a Schlemm's canal ho-
     cessfully eliminated the subsequent time-de-         mology.3 On the other hand, the remaining
     pendent increase in facility (washout) in only       component of cyclotonic-induced facility in-
     four of the six control eyes. This meant that a      creases in the primate probably derives from
     portion of the hyaluronidase-sensitive com-          a direct effect on the trabecular meshwork
     ponent persisted in some eyes even after in-         itself.14 In previous lens depression experi-
     tracameral hyaluronidase irrigation and that          ments in primates, an attempt was made to
                                                                                                Invest. Ophthalmol. Vis. Sci.
    792 Van Buskirk                                                                                                July 1980

    differentiate the portions of facility increases                glaucoma in the beagle. INVEST OPHTHALMOL VI-
                                                                     SUAL SCI 16:1135, 1977.
    resulting from induction of circumferential
                                                                 7. Kaufman PL and Barany EH: Loss of acute pilocar-
    flow and from a direct effect on trabecular                     pine effect on outflow facility following surgical dis-
    meshwork. Interestingly, the magnitude of                       insertion and retrodisplacement of the ciliary mus-
    the total lens depression-induced facility in-                  cle from the scleral spur in the cynomolgus monkey.
    crease in the dog is less than the total effect of               INVEST OPHTHALMOL 15:793, 1976.

    lens depression in primate eyes but is quanti-                8. Van Buskirk EM and Grant VVM: Lens depression
                                                                     and aqueous outflow in enucleated primate eyes.
    tatively comparable to the trabecular compo-                     Am J Ophthalmol 76:632, 1973.
    nent of facility increases in the primate.8                   9. Van Buskirk EM: Changes in the facility of aqueous
       In spite of many important anatomic and                       outflow induced by lens depression and intraocular
    physiologic differences between the aqueous                      pressure in excised human eyes. Am J Ophthalmol
    outflow systems of the primate and canine                        82:736, 1976.
                                                                 10. Epstein DL, Hashimoto JM, and Grant WM: Serum
    eyes, they appear to share some aspects of                       obstruction of aqueous outflow in enucleated eyes.
    these responses to mechanical tension on                         Am J Ophthalmol 86:101, 1978.
    their respective filtration mesh works.                      11. Grant WM: Further studies on facility of flow
                                                                     through the trabecular meshwork. Arch Ophthalmol
                                                                     60:523, 1958.
        REFERENCES                                               12. Rohen JW, Liitjen E, and Barany E: The relation
     1. Van Buskirk EM and Brett J: The canine eye: in               between the ciliary muscle and the trabecular
        vitro dissolution of the barriers to aqueous outflow.        meshwork and its importance for the effect of mi-
        INVEST OPHTHALMOL VISUAL SCI 17:258, 1978.                   otics on aqueous outflow resistance. A study in two
     2. Van Buskirk EM and Brett J: The canine eye: in               contrasting monkey species, Macaco irus and Cer-
        vitro studies of the intraocular pressure and facility       copithecus aethiops. Albrecht von Graefes Arch Klin
        of aqueous outflow. INVEST OPHTHALMOL VISUAL SCI             Exp Ophthalmol 172:23, 1967.
        17:373, 1978.                                            13. Barany EH, Linner E, Liitjen-Drecoll E, and
     3. Van Buskirk EM: The canine eye: the vessels of               Rohen JW: Structural and functional effects of
        aqueous   drainage.   INVEST OPHTHAL VISUAL SCI              trabeculectomy in cynomolgus monkeys. Albrecht
        18:223, 1979.                                                von Graefes Arch Klin Exp Ophthalmol 184:1, 1972.
     4. Gelatt KN, Peiffer RL Jr, Gwin RM, and Sauk JJ Jr:       14. Barany EH: The influence of extraocular venous
        Glaucoma in the beagle. Trans Am Acad Ophthal-               pressure on outflow facility in Cercopithecus ethiops
        mol Otolaryngol 81:636, 1976.                                and Macaca fascicularis.    INVEST OPHTHALMOL VI-
     5. Gelatt KN: Animal models for glaucoma. INVEST                SUAL SCI 17:711, 1978.
        OPHTHALMOL VISUAL SCI 16:592, 1977.                      15. Nesterov AP, Hasanova NH, and Batmanov YE:
     6. Gelatt KN, Peiffer RL Jr, Gwin RM, Gum GG, and               Schlemm's canal and scleral spur in normal and
        Williams LW: Clinical manifestations of inherited            glaucomatous eyes. Acta Ophthalmol 52:634, 1974.

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