Drugs designed to maintain the transparence of the ocular lens

Abstract

Research into the biological basis of lens transparency has demonstrated the implication of lens sugar stress in the diabetic cataract whereas senile cataract is the result of natural degeneration which is enhanced by various external factors such as cosmic and ionizing rays, or oxidative processes. Drugs have been developed which are aimed at being effective on lens pathological physiology and metabolism, concurrently. Such molecules: aldose reductase inhibitors (ARIs: sorbinil, AD-5467, CT-112 and imirestat), acetyl salicylic acid (ASA), salicylate (SA) and sodium monomethyl trisilanol orthohydroxybenzoate (SMB, a prodrug for salicylate) have undergone pharmacodynamic, pharmacokinetic and/or clinical studies which are presented here. ARIs have shown efficacy in slowing down and preventing the progression of experimental sugar cataracts; sorbinil can partially reverse the very early morphological signs of sugar cataract. Sorbinil and imirestat have also demonstrated anti-oxidant properties. ARIs administration (per os or by topical instillation) generally results in lens levels compatible with concentrations that are efficient on biochemical mechanisms of cataract formation. However, at the present time, clinical evaluations are in progress and as yet, there is no confirmation of their efficacy in man. ASA and SA can prevent various mechanisms of lens protein denaturation; they inhibit AR and prevent, in vitro, the formation of some pigments found in the aged cataractous lens. Extrapolation of the ASA ocular pharmacokinetics results in animal to man, suggest that ASA administration per os could result in efficacious levels in the lens. This is also sustained by the observation of a reduced frequency of cataracts in ASA treated diabetic rheumatoid arthritis patients. SMB pharmacokinetic studies have shown small but persistent levels of the active principle in the lens. They suggest that the capsule slows down SA diffusion into the lens and that, on the contrary, lens epithelium facilitates its penetration. Preliminary results of pharmacodynamic studies are given.