晶状体发育异常可引起眼前段发育不良（Anterior segment dysgenesis，ASD)，如先天性白内障、小眼球畸形, Peters异常等，已成为儿童致盲的主要原因之一。项目申请人多年来一直致力于Msx2基因在眼发育过程中的调控机制研究。研究发现，晶状体组织特异性Msx2条件基因敲除小鼠（Msx2cko, 轻表型）与人ASD中Peters异常表型相似；晶状体胚胎发育早期FoxE3表达下调，Prox1表达增加；晶状体细胞增殖减少、凋亡增加；激活Caspase3/Caspase8信号通路及钙信号通路等。本研究拟采用AAV9介导的Msx2基因过表达的病毒载体系统，经尾静脉注射入Msx2ko（Msx2传统基因敲除）和Msx2cko孕鼠体内，使Msx2基因过表达挽救晶状体发育异常的表型，为晶状体发育异常的子宫内基因治疗提供新的理论和实验依据。

Lens abnormal development can cause anterior segment dysgenesis, including congenital cataract, microphthalmia, Peters anomaly and has become one of the major cause of blindness in children. Applicant had years of research experience in abnormal lens development related to Msx2 gene mutation. The study found that lens-specific conditional knockout of Msx2 in mice(Msx2 cko, mild phenotype) led to ocular anterior segment dysgenesis, similar to peters anomaly, an increased apoptosis rate, a significant reduction in FoxE3 expression, and an up-regulation of Prox1 expression in the lens vesicle during the early embryonic period. This study intends to use AAV9 mediated Msx2 overexpression to rescue the abnormal lens phenotype by injecting the vector system into Msx2ko (Msx2 traditional gene knockout) and Msx2cko pregnant mice via the tail vein, which will provides theoretical basis and experimental supporting intrauterine gene therapy of abnormal lens development.