Model of ionic transport for bovine ciliary epithelium: Effects of acetazolamide and HCO₃^-

The possible existence of transepithelial bicarbonate transport across the isolated bovine ciliary body was investigated by employing a chamber that allows for the measurement of unidirectional, radio-labeled fluxes of CO2 + HCO3-. No net flux of HCO3- was detected. However, acetazolamide (0.1 mM) reduced the simultaneously measured short-circuit current (Isc). In other experiments in which 36Cl- was used, a net Cl- flux of 1.12 μeq·h-1·cm-2 (30 μA/cm2) in the blood-to-aqueous direction was detected. Acetazolamide, as well as removal of HCO3- from the aqueous bathing solution, inhibited the net Cl- flux and Isc. Because such removal should increase HCO3- diffusion toward the aqueous compartment and increase the Isc, this paradoxical effect could result from cell acidification and partial closure of Cl- channels. The acetazolamide effect on Cl- fluxes can be explained by a reduction of cellular H+ and HCO3- (generated from metabolic CO2 production), which exchange with Na+ and Cl- via Na+/H+ and Cl-/HCO3- exchangers, contributing to the net Cl- transport. The fact that the net Cl- flux is about three times larger than the Isc is explained with a vectorial model in which there is a secretion of Na+ and K+ into the aqueous humor that partially subtracts from the net Cl- flux. These transport characteristics of the bovine ciliary epithelium suggest how acetazolamide reduces intraocular pressure in the absence of HCO3- transport as a driving force for fluid secretion.