NOVEL TOPICAL THIADIAZOLES AND BENZOTHIAZOLES AS PHARMACOLOGICAL PROBES OF CORNEAL ENDOTHELIAL FUNCTION

Corneal transparency is maintained by an active transport system, loca ted at the endothelial cell membranes. This bicarbonate-dependent pump counteracts the tendency of the corneal stroma to absorb water, swell and become opaque. Carbonic anhydrase inhibitors (CAI) are capable of attenuating the bicarbonate efflux, therefore causing thickening of t he cornea. Eight novel sulfonamides were evaluated as potential probes for assessing the corneal endothelial functional reserves. Five of th e six thiadiazoles and both benzothiazoles have demonstrated carbonic anhydrase inhibitory properties in vitro. Of the eight compounds teste d, 2-ethyladipoyl-1,3,4-3,4-thiadiazole-5-sulfonamide (compounds III), 2-epoxy-1,3,4-thiadiazole-5-sulfonamide (compound V), and -acetamido- 1,3,4-thiadiazole-5-N-methylsulfonamide (compound VI) have induced rev ersible corneal thickening. Although statistically significant (p < 0. 05), the magnitude of the pachymetric effect did not exceed 6-10% of t he total corneal thickness, probably because carbonic anhydrase (CA) i s only one component of the active pump complex. The fact that a non-C AI (compound VI) was capable of inducing a reversible corneal thickeni ng may suggest that other mechanisms are involved. Further studies wil l. be conducted to identify a pharmacological agent capable of reversi bly inhibiting the endothelial function in normal and diseased corneas , with a higher magnitude of effect.