Carbonic Anhydrase Inhibitors in Corneal Endothelial Transport

PURPOSE. Carbonic anhydrases play a central buffering role in current models of fluid transport in corneal endothelium, but in humans, clinical use of carbonic anhydrase inhibitors (CAIs) for the management of glaucoma does not cause corneal swelling. This study compares species differences in response to CAIs in human versus bovine corneal endothelial transport. METHODS. Short-circuit current (I-sc) measurements were performed on bovine and human corneal endothelium under identical conditions. The effects of four CAIs (acetazolamide, brinzolamide, dorzolamide, and ethoxzolamide) were measured. Endothelial expression of carbonic anhydrase II and IV was evaluated by immunofluorescence microscopy. Functional presence of carbonic anhydrase activity was determined using the Hansson's cobalt sulfide histochemical method. RESULTS. All four CAIs decreased bovine Isc (% change in Isc: acetazolamide, -21.0 +/- 9.5, n = 8; brinzolamide, -35.5 +/- 13.5, n = 9; dorzolamide, -33.6 +/- 7.2, n = 8; ethoxzolamide, -35.3 +/- 12.9, n = 8). That decrease was not present in humans (% change in I-sc: acetazolamide, 16.2 +/- 20.1, n = 3; brinzolamide, 6.7 +/- 13.9, n = 3; dorzolamide, 8.0 +/- 20.4, n = 3; ethoxzolamide, -4.8 +/- 10.3, n = 2). Despite no functional effect of CAIs on I-sc, both carbonic anhydrase II and IV were present in human corneal endothelium by immunofluorescence microscopy. Histochemical analysis of human corneal endothelium revealed functionally active carbonic anhydrase activity inhibited by brinzolamide. CONCLUSIONS. Carbonic anhydrase facilitates ion transport impacting the corneal endothelial Isc in bovine but not human corneal endothelium, despite its presence and functional activity in human tissue. This finding supports the clinical observation of no corneal swelling in humans administered CAIs and suggests that alternative ion transport mechanisms may be operational in corneal endothelium of different species.