Novel topical thiadiazoles and benzothiazoles as pharmacological probes of corneal endothelial function.

Corneal transparency is maintained by an active transport system, located 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 the cornea. Eight novel sulfonamides were evaluated as potential probes for assessing the corneal endothelial functional reserves. Five of the six thiadiazoles and both benzothiazoles have demonstrated carbonic anhydrase inhibitory properties in vitro. Of the eight compounds tested, 2-ethyladipoyl-1,3,4-thiadiazole-5-sulfonamide (compounds III), 2-epoxy-1,3,4-thiadiazole-5-sulfonamide (compound V), and 2-acetamido-1,3,4-thiadiazole-5-N-methylsulfonamide (compound VI) have induced reversible corneal thickening. Although statistically significant (p < 0.05), the magnitude of the pachymetric effect did not exceed 6-10% of the total corneal thickness, probably because carbonic anhydrase (CA) is only one component of the active pump complex. The fact that a non-CAI (compound VI) was capable of inducing a reversible corneal thickening may suggest that other mechanisms are involved. Further studies will be conducted to identify a pharmacological agent capable of reversibly inhibiting the endothelial function in normal and diseased corneas, with a higher magnitude of effect.