DRUGS DESIGNED TO MAINTAIN THE TRANSPARENCY OF THE OCULAR LENS

Research into the biological basis of lens transparency has demonstrat ed the implication of lens sugar stress in the diabetic cataract where as senile cataract is the result of natural degeneration which is enha nced by various external factors such as cosmic and ionizin,o rays, or oxidative processes. Drugs have been developed which are aimed at bei ng effective on lens pathological physiology and metabolism, concurren tly. Such molecules: aldose reductase inhibitors (ARIs: sorbinil, AD-5 467, CT-112 and imirestat), acetyl salicylic acid (ASA), salicylate (S A) and sodium monomethyl trisilanol orthohydroxybenzoate (SMB, a prodr ug for salicylate) have undergone pharmacodynamic, pharmacokinetic and /or clinical studies which are presented here. ARIs have shown efficac y in slowing down and preventing the progression of experimental sugar cataracts; sorbinil can partially reverse the very early morphologica l signs of sugar cataract. Sorbinil and imirestat have also demonstrat ed anti-oxidant properties. ARIs administration (per os or by topical instillation) generally results in lens levels compatible with concent rations that are efficient on biochemical mechanisms of cataract forma tion. However, at the present time, clinical evaluations are in progre ss and as yet, there is no confirmation of their efficacy in man. ASA and SA can prevent various mechanisms of lens protein denaturation; th ey inhibit AR and prevent, in vitro, the formation of some pigments fo und in the aged cataractous lens. Extrapolation of the ASA ocular phar macokinetics results in animal to man, suggest that ASA administration per os could result in efficacious levels in the lens. This is also s ustained by the observation of a reduced frequency of cataracts in ASA treated diabetic rhumatoid arthritis patients. SMB pharmacokinetic st udies have shown small but persistent levels of the active principle i n the lens. They suggest that the capsule slows down SA diffusion into the lens and that, on the contrary, lens epithelium facilitates its p enetration. Preliminary results of pharmacodynamic studies are given.