Lens proteins once formed show little or no turnover. This is essential since lens fiber cells lose their protein synthetic ability with time. Consistent with the low protein turnover, there is little endopeptidase activity in lens cortical extracts. We have proposed that this lack of proteolytic activity is not due to a lack of proteinases, but rather that these enzymes are held in an inactive state by the presence of endogenous proteinase inhibitors. This could explain how proteolysis can be seen in cataractous lenses. During cataract formation a loss of inhibitor activity would lead to release of active proteinases which degrades lens proteins and ultimately results in liquefaction of the lens matrix in hypermature cataracts. We have initiated a study to demonstrate proteinase inhibitors in the lens and to show that if these inhibitors are inactivated, one can measure the release of active proteinase. Bovine lens extracts contain 2 and possibly 4 different trypsin inhibitor proteins, and if these inhibitors are inactivated as in the lens nucleus in vivo or by chemical treatment in vitro, one can see trypsin-like proteolytic activity. Furthermore, these proteinases can be separated into 3-5 different peaks by Agarose gel filtration. Several of these proteinases have been purified and each has different properties. All these enzymes, however, appear to be serine proteinases. The interaction between these proteinases and the lens inhibitors may provide an insight into the chemical mechanisms involved in cataractogenesis.
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