CALCIUM IONOPHORE-INDUCED PROTEOLYSIS AND CATARACT - INHIBITION BY CELL-PERMEABLE CALPAIN ANTAGONISTS

Two dipeptide aldehyde cell permeable calpain inhibitors, cBz-Val-Phe and calpeptin, have been assessed for their ability to prevent cytoske letal proteolysis and loss of transparency in whole rat lenses. Calciu m overload, induced by ionomycin in artificial aqueous humor with lmM calcium, resulted in lens opacification and degradation of cytoskeleta l proteins including spectrin, filensin, and vimentin. No such changes resulted from incubation in ionomycin in the absence of calcium. In c alcium overload lenses both inhibitors gave some protection against cy toskeletal protein degradation and loss of transparency. These experim ents indicate that calpain has a role in cortical opacification in hig h calcium lenses and that cell penetrating calpain inhibitors do indee d enter lens cells and reduce both proteolysis and opacification. (C) 1996 Academic Press, Inc.