Abstract
The effects of carbonic anhydrase inhibition on the transepithelial potential (TEP) generated by the ciliary epithelium were invesigated using a specially prepared and isolated ciliary epithelial bilayer tissue from the rabbit eye.
The TEP was -733±34μV, aqueous side negative. The TEP is very largely bicarbonate dependent because, in bicarbonate free media, with a stabilized pH, the potential declines to zero. The carbonic anhydrase inhibitors (CAIs) acetazolamide, methazolamide, MK927, and ethoxzolamide decreased the TEP to 70-80% of baseline values when added on the blood (stromal) side (PE surface) of the preparation. When these inhibitors were added to the aqueous side (NPE surface), the decrease in the amplitude of the TEP was not much different. The magnitude of the decline corresponds very well to the percentage decrease in the rate of sodium entry into the posterior chamber after systemic carbonic anhydrase inhibition reported by others. These relatively lipophilic CAIs probably affect cytosolic carbonic anhydrase of the PE and/or NPE. Benzolamide, however, another carbonic anhydrase inhibitor that completely dissociates at neutral pH and hardly penetrates the cell, was considerably more effective from the aqueous side, suggesting that its effect is membranal, i. e., on a basolateral membranal carbonic anhydrase of the NPE. To test this hypothesis, quaternary ammonium sulfanilamide (QAS), a weak membrane impermeant CAI, was used. QAS caused a significant drop in the TEP but only when added from the aqueous (NPE) side. These results indicate that there is a membrane bound carbonic anhydrase associated with the basolateral membrane of the nonpigmented ciliary epithelial cells.
