α-crystallins是眼睛晶状体结构蛋白，对眼睛功能起着十分重要的作用，其编码基因突变导致重要的致盲疾病—白内障。目前，虽然白内障可以通过手术来恢复视力，但术后综合症给病人带来显著的困扰和经济负担。因此，对白内障发病机制及其有效治疗的研究对改善国民健康，提高生活质量有着重要的临床和经济意义。我们之前的研究表明，α-crystallins调节多个靶分子和多条信号通路抑制细胞凋亡，阻止白内障发生。但α-crystallins调节这些靶分子和信号通路的分子机制则有待深入研究。本项目旨在用现代生物学的方法来确定 1) α-crystallins调节不同靶分子和信号通路的分子机制；2) α-crystallins表达和功能的改变与白内障形成之间的关系；3) α-crystallins用于白内障治疗是否有效。本项目研究的结果期待为了解白内障的发病机制带来崭新的信息，并为它们的治疗提供新的可能性。

Alpha-Crystallins are the structural proteins of the ocular lens, and play fundamental roles in the eye. Mutations in the coding genes for alpha-crystallins cause blindness, a major ocular disease called cataract. Cataract causes blindness of nearly 20 millions people around the world. Although with surgical operation, cataract can be corrected with implanted artificial plastic lenses, post-operation syndromes including posterior subcapsular cataract often brings about interference with vision and additional economic burden to the affected patients. Therefore, it is both clinically significant and economically important to have a comprehensive understanding of the mechanisms mediating cataractogenesis so that better therapeutic strategies for cataract treatment can be developed. Our previous studies have revealed that alpha-crystallins can bind to various targets and regulate different signal transduction pathways to resist induced apoptosis followed by cataractogenesis. However, the exact molecular mechanisms by which alpha-crystallins exert their functions remain to be further investigated. In this application, we propose to use modern technology and transgenic mice as testing systems to determine 1) How do alpha-crystallins regulate different signaling pathways to resist abnormal apoptosis and subsequent cataractogenesis; 2) Whether a change in the functional status or expression level of alpha-crystallins plays an important role in cataractogenesis? 3) If alpha-crystallins can be modified into efficient therapeutic drugs to prevent or reverse cataractogenesis. The obtained results from this application will generate novel information regarding the mechanisms mediating cataratogenesis and also provide possible new strategy to treat cataract.