Sulfonamides and secretion of aqueous humor

The connection between carbonic anhydrase and the formation of aqueous humor arose in the decade 1950-1960 when a number of experiments of differing types showed that HCO3- ion catalytically formed in the ciliary process from CO2 was a principal element in the production of the aqueous. It was soon shown that inhibitors of the enzyme, given systemically, slowed HCO3- formation and sodium and fluid transport and thereby lowered intraocular flow and pressure in normal vertebrates and in patients with glaucoma. In the past 15 years successful efforts have been made to produce sulfonamide inhibitors that reach the ciliary process after local application to the cornea. The effects of locally acting sulfonamides are largely due to their amphoteric properties. They are soluble in both lipid and non-lipid media and penetrate cornea and sclera to reach ciliary process. Potency against carbonic anhydrase II is of the order of K(I) = 10(-9) M, so that topical application inhibits essentially all enzyme in the processes and is an effective nontoxic treatment for glaucoma.