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.