内质网应激（ERS）与许多退行性疾病有关，体外研究发现其参与晶状体上皮细胞（LECs）的凋亡。蛋白质在内质网的合成、修饰异常时将激活ERS，启动未折叠蛋白应答（UPR），恢复内质网稳态。但当ERS反应过度时，UPR将诱导线粒体损伤，并随着线粒体损伤的进一步加重而介导细胞凋亡。UPR的三种应激感受器均具有差异化调控的功能，它同时具有恢复内质网稳态和促进细胞凋亡的作用。因此，维持LECs内质网的适度应激，将是白内障预防和治疗的关键。我们前期研究发现，白内障组ERS标志蛋白CHOP、Caspase-12、GRP78表达与透明晶状体组有显著差异，说明白内障LECs内ERS上调并且凋亡通路激活；本课题我们将建立动物模型，并系统评估ERS对晶状体的影响，并通过差别化调控IRE1、PERK、Ca2+相关蛋白以及ERS相关凋亡蛋白的功能，探讨ERS及其诱导的线粒体损伤在白内障发病机制中的作用。

Cataract is the main cause of blindness. Endoplasmic reticulum stress (ERS) is associated with many neurodegenerative diseases, and studies found that it may participate in the apoptosis of lens epithelial cell (LECs) in vitro. When the synthesis and modification of proteins in the endoplasmic reticulum is abnormal, the ERS will be activated. Then the unfolded protein response (UPR) starts to recovery the homeostasis of endoplasmic reticulum. But when ERS is over reaction, UPR mediates apoptosis. IRE1 is one of the three stress-receptors of UPR, and it has bidirectional regulation. It could restore the endoplasmic reticulum homeostasis or promote cells apoptosis. Therefore,to maintain the moderate ERS of LECs, will be the key to the prevention and treatment of cataract. Our previous study found that, there was significant difference in the expression of ERS markers (protein-CHOP, Caspase-12, GRP78) between the cataract group and the transparent lens group. It shows that ERS up regulates and activates the apoptosis pathway in cataract LECs. In this issue, We will establish an animal model,we will systematically evaluate the role of ERS on the lens. We also investigate the role of IRE1, PERK, Ca2+ related protein and ERS-related apoptosis proteins in cataract pathogenesis by regulating the ERS of LECs at different level, and try to find the underlying molecular mechanism of ERS -induced mitochondrial injury and its regulatory in age-related cataract.