Calpains: targets of cataract prevention? Biswas S, Harris F, Dennison S, Singh J, Phoenix DA. Trends in Mol Med 2004;10:78–84

Abstract

There is emerging evidence to suggest that the unregulated Ca2+-mediated proteolysis of essential lens proteins by calpains might be a major contributor to some forms of cataract in both animals and humans. Based on current evidence, calpain 2 appears to be the major calpain involved in animal models of diabetic cataractogenesis, and the only major calpain active in human lenses. Although current research has not definitively demonstrated a role for calpain 2 in human cataract, the results available strongly suggest a major contribution of calpain 2 to at least some forms of human cataract. Moreover, recently solved calpain structures have revealed molecular-level details of the activation mechanism used by these proteases, enabling the structure-based design of potent calpain inhibitors with the potential to act as anti-cataract agents. Based on the aldehyde SJA601y, significant advances are being made in the development of calpain inhibitors that have anti-cataract ability and physiochemical properties suitable for topical administration to the eye.