CALCIUM ACTIVATED PROTEASE IN CATARACT FORMATION

这项研究的长期目标是了解 钙激活蛋白水解酶(CAP)在正常晶状体成熟和晶状体发育中的作用 白内障的形成。据我们所知，我们有第一个 初步数据显示CAP在年轻人和猴子中存在 隐形眼镜。我们将进行实验，以验证我们的工作假设 晶状体CAP通常与晶状体成熟有关。我们将测试CAP是否 参与老年性白内障的发生，因为CAP活性随着 老化，导致受损的蛋白质聚集并形成混浊。实验 将进行测试，以测试激活CAP在 在几种动物身上形成几种实验性白内障，以及 这将允许将履约协助方案作为发展中的一个可能因素进行评估。 在相对年轻的人类晶状体中观察到的白内障。 提出了七个实验：1)纯化和表征 人、猴、兔、鼠和牛晶状体中的CaP及其抑制物，2) CAP及其抑制物在不同类型晶状体中的区域分布 动物种类，3)CAP天然底物的测定，4) CAP在人晶状体中的免疫学定位和定量， 5)温育全晶状体中CAP的激活作用；6)CAP的作用 在各种实验性白内障中，以及7)CAP抑制剂作为 预防白内障的药物疗法。来自这些实验的数据应该 展示CAP在正常和正常对照中的生物学功能和调控 白内障镜片。希望这样的知识将被用来理解 并预防人类白内障的形成。

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.