后发性白内障（PCO）是白内障摘出联合人工晶状体(IOL)植入术后最常见并发症，由囊袋上皮细胞增生、迁徙和纤维化而致。我们发现外泌体和αB-crystallin组成囊袋微环境，αB-crystallin存在于外泌体中，外泌体抑制剂可延缓大鼠PCO发生。由此，推测αB-crystallin调控外泌体分泌，后者介导特异microRNA或细胞生长因子，参与PCO囊袋残留上皮细胞间的信号传递。该立项以大鼠、αB-crystallin 敲除小鼠晶状体囊袋和恒河猴PCO模型为材料，深入研究：1）不同年龄大鼠或恒河猴晶状体囊袋微环境中外泌体的蛋白和microRNA组学以及它们对PCO形成的调控作用；2）外泌体介导EGFR和TGFR信号通路对PCO发生和发展的调控机制；3）αB-crystallin对外泌体分泌的调控机制以及调控PCO发生、发展的生理意义。目的：揭示外泌体调控PCO发生、发展的分子和机制。

Posterior capsule opacification (PCO), which is the most common complication after cataract extraction combining with intraocular lens (IOL) implantation, is resulted from the combining processes of proliferation, migration and fibrosis of capsular epithelial cells, and the whole processes are regulated by capsular microenviroment,which consists of TGF-beta, FGF2, EGF and inflammatory cytokines.Our preliminary data showed that exosome and alpha B-crystallin constitutes the capsular microenvironment,and alpha B-crystallin exsits within the exosome.The inhibition of exosome by GW 4869 delays PCO formation in rat model. Accordingly, we postulated that alpha B-crystallin regulates the secretion of exosome,the latter regulates the proliferation, EMT (epithelial-mysenchymal transition),migration and fibrosis of capsular residual epithelial cells by integrating the signals of exosomic micro-RNA and growth factors.In this grand application, we will utlize the PCO models of rats, rabbit and rhesus money,alpha B-crystallin knocking out mice to study extensively the following questions: 1) proteomic and microRNA array study of rat capsular microenviromental exsosomes at different ages to identify the key components that regulate PCO development; 2) The regulatory association of exosome and growth factor receptors such as EGFR and TGFR in the regulation of the proliferation and migration of capsular residual cells in rat PCO model ex vivo; 3) The molecular mechanism underlying the exosome secretion regulated by alpha B-crystallin and the physiological significance of this regulation in PCO initiation and development. The objective is to uncover the molecular and mechanism underlying the exosome regulation on PCO’s occurrence and development.