CALCIUM ACTIVATED PROTEASE IN CATARACT FORMATION

这项研究的长期目标是了解 在正常透镜成熟和晶状体上皮细胞中， 白内障的形成。 据我们所知，我们有第一个 初步数据表明CAP存在于年轻人和猴子中 眼镜. 将进行实验来检验我们的工作假设， 透镜CAP通常参与透镜成熟。 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，导致受损蛋白质聚集并形成不透明。 实验 将进行测试，以测试CAP激活在 在几种动物物种中形成几种实验性白内障，以及 这将有助于评估联合呼吁程序，将其作为发展的一个可能因素 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、大鼠和牛晶状体中的CAP及其抑制剂，2） CAP及其抑制剂在各种晶状体中的区域分布 动物种属，3）CAP天然底物的测定，4） CAP在人透镜内的免疫定位和定量， 5)在孵育的整个透镜内CAP活化的影响，6）CAP的作用 在各种实验性白内障中，以及7）CAP抑制剂作为 预防白内障的药物治疗。 这些实验的数据应该 证明CAP的生物学功能和控制， 白内障晶状体 希望这些知识能被用来理解 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.