CALCIUM ACTIVATED PROTEASE IN CATARACT FORMATION

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.