CALCIUM ACTIVATED PROTEASE IN CATARACT FORMATION

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The long-term objective of this research is to understand the role of the enzyme, calcium-activated protease (CAP), in normal lens maturation and in the formation of cataracts. To our knowledge, we have the first preliminary data to show that CAP is present in young human and monkey lenses. Experiments will be performed to test our working hypothesis that lens CAP is normally involved in lens maturation. We will test if CAP is involved in senile cataractogenesis, because CAP activity is lost with aging, causing damaged proteins to aggregate and form opacity. Experiments will be performed to test the role of activation of CAP during the formation of several experimental cataracts in several animal species, and this will allow evaluation of CAP as a possible factor in the development of cataracts observed in relatively young human lenses. Seven experiments are proposed: 1) purification and characterization of CAP and its inhibitor in human, monkey, rabbit, rat, and bovine lenses, 2) regional distribution of CAP and its inhibitor within the lenses of various animal species, 3) determination of natural substrates of CAP, 4) immunological localization and quantitation of CAP within the human lens, 5) effects of activation of CAP within incubated whole lens, 6) role of CAP in various experimental cataracts, and 7) efficacy of CAP inhibitors as drug therapy to prevent cataracts. Data from these experiments should demonstrate the biological function and control of CAP in normal and cataractous lenses. Hopefully, such knowledge will be used to understand and prevent cataract formation in man.