GENETIC DETERMINANTS OF CATARACT

项目摘要 晶状体透镜在脊椎动物的前眼发育和屈光视觉中起着中心作用。损失 透镜透明或白内障是临床上重要的低视力原因，尽管进行了手术治疗， 仍然是全球失明的主要原因（约40%）。通常，白内障是随着年龄的增长（>40岁）而获得的， 涉及环境和遗传风险因素的多因素或复杂疾病。此外，白内障可能 遗传为孟德尔疾病，通常在青少年发病，许多小鼠模型的人类白内障 已经描述了虽然已经确定了年龄相关性白内障的几个环境风险因素， 关于遗传因素的性质和确切作用知之甚少，据估计，遗传因素占到了50%左右。 风险然而，越来越多的证据表明，遗传性白内障的基因也参与其中。 老年性白内障这项研究的总体目标是促进对分子生物学的理解。 导致白内障的机制/途径。具体来说，我们建议确定新的基因遗传形式 在人类白内障的发病机制，并确定在人类年龄相关性白内障小鼠模型的致病基因 使用分子遗传学和基因组学技术的组合。这些研究结果将提供新的 关于透镜发育、衰老和白内障发生的分子基础的见解，最终可能 有助于发现延迟、逆转甚至预防白内障形成的非手术方法。

Project Summary The crystalline lens plays a central role in vertebrate anterior eye development and refractive vision. Loss of lens transparency, or cataract(s), is a clinically important cause of low vision that despite surgical treatment remains a leading cause (~40%) of blindness worldwide. Typically, cataract is acquired with aging (>40 yrs) as a multi-factorial or complex disorder involving environmental and genetic risk factors. In addition, cataract may be inherited as a Mendelian disorder usually with juvenile-onset, and many mouse models of human cataract have been described. While several environmental risk factors have been established for age-related cataract, little is known about the nature and precise role of genetic factors that are estimated to account for ~50% of the risk. However, there is increasing evidence that genes underlying inherited forms of cataract are also involved in age-related cataract. The overall goal of this research is to advance understanding of the molecular mechanisms/pathways that lead to cataract. Specifically, we propose to identify novel genes for inherited forms of cataract in humans, and to identify the causative gene in a mouse model of human age-related cataract using a combination of molecular genetic and genomic techniques. Results from these studies will provide new insights about the molecular basis of lens development, aging and cataractogenesis, and ultimately may contribute to the discovery of non-surgical means to delay, reverse or even prevent cataract formation.