EVIDENCE FOR THE INVOLVEMENT OF CALPAIN IN CATARACTOGENESIS IN SHUMIYA CATARACT RAT (SCR)

The Shumiya cataract rat (SCR) is a hereditary cataract model in which lens opacity appears spontaneously in the nuclear and perinuclear por tions at 11-12 weeks of age. It was found that the proteolysis of some crystallins and cytoskeletal proteins is significantly enhanced in ca taractous SCR lenses. The calcium concentrations in cataractous lenses rise markedly with age as compared with control lenses and the autoly tic product of calpain is also detected in cataractous lenses, In orde r to provide direct evidence for the involvement of calpain in the pro teolytic modification of lens proteins, we developed antibodies exclus ively specific to the proteolytic products of some lens proteins produ ced by the action of calpain and analyzed their degradation during cat aractogenesis in SCR by Western blotting and immunohistochemical stain ing. The results demonstrate that calpain participates in the proteoly tic modification of lens proteins, at least alpha-crystallin (A and B chain), beta B1-crystallin, and alpha-fodrin. The proteolytic products formed by the action of calpain on these proteins are detected in cat aractous lenses of SCR as young as 8 weeks of age and accumulate with age. It was also found that beta B1-crystallin, originally a soluble p rotein, is converted to an insoluble form by limited calpain proteolys is. The chaperon-like activity of alpha-crystallin from control lens i s markedly reduced by calpain proteolysis in vitro, and alpha-crystall in in opaque lens that has already undergone proteolysis by calpain sh ows significantly reduced chaperon-like activity. Immunohistochemical studies reveal that the area where the calpain-mediated alpha-crystall in proteolysis is in progress coincides well with the area developing and destined to develop the opacification. These results strongly sugg est that calpain may contribute to lens opaciication during cataract f ormaiton in SCR. (C) 1997 Elsevier Science B.V.