chloride_channels

							  CHLORIDE CHANNELS AND AQUEOUS HUMOR FORMATION: WHERE,
                                      WHY, HOW?

    Chi Wai Do1,3, Zhao Wang1, Kim Peterson-Yantorno1 and Mortimer M. Civan1,2

    Departments of Physiology1 and Medicine2, University of Pennsylvania School of
     Medicine, Philadelphia, United States; School of Optometry3, The Hong Kong
                      Polytechnic University, Kowloon, Hong Kong.



Aqueous humor is secreted by the ciliary epithelium comprising pigmented (PE) and non-
pigmented epithelium (NPE) facing the stroma and aqueous humor, respectively. Net Cl-
secretion likely limits the rate of aqueous inflow and proceeds in three steps: stromal Cl-
uptake into PE cells, diffusion to NPE cells where Cl- exits into the aqueous humor. Cl-
channels in isolated PE and NPE cells have demonstrated distinct properties and have
been shown to modulate Cl- secretion and thereby aqueous humor formation. At the
stromal surface, cAMP-activated maxi-Cl- channels can recycle Cl-, reducing net Cl-
secretion. At the aqueous-humor surface, swelling- (ICl,swell) and A3 adenosine-receptor-
(A3AR) activated Cl- channels subserve Cl- release into the aqueous humor. The similar
macroscopic properties of the two NPE cell Cl- currents suggest that both flow through a
common conduit. Recently, we have demonstrated that the stimulation of ICl,swell in NPE
cells increases the short-circuit current across the intact ciliary epithelium, leading to an
increased Cl- secretion. The time course of the hypotonically-triggered stimulation of
short-circuit current is comparable to that of the regulatory volume decrease in isolated
NPE cells, suggesting that the swelling-activated Cl- channels are predominantly
localized at the aqueous surface of NPE cells and its net effect is to enhance aqueous
humor formation. Consistent with the electrophysiologic and volumetric findings,
measurements of intraocular pressure (IOP) in living wild-type and mutant mice have
confirmed that A3AR agonists and antagonists increase and lower IOP, respectively.
Taken together, our results suggest that Cl- channels in the ciliary epithelium are
important in the understanding of aqueous humor secretion and its regulation. The
regulation of its activities will likely modulate the aqueous inflow and eventually IOP.