AQP5通过miRNAs介导的细胞自噬对晶状体透明性的保护机制

白内障是临床上主要的致盲性眼病，发病机制多样。水通道蛋白5(AQP5)参与晶状体透明性的维持，但其作用机制尚不清楚，也无AQP5突变引起白内障的报道。我们前期在遗传性白内障家系中发现了AQP5的致病突变；且AQP5敲除小鼠，晶状体也出现了明显混浊，其晶状体上皮细胞内自噬水平下降，波形蛋白表达增多且聚集分布；在AQP5敲除小鼠晶状体的miRNAs表达芯片中，调控细胞自噬的miR-20a、miR-30a和miR-106b表达显著上调。在此基础上我们提出：AQP5可能通过miR-20a、miR-30a和miR-106b调控细胞自噬参与维持晶状体的透明性。本项目将以自噬为切入点，利用晶状体囊袋培养、AQP5敲除小鼠及致病突变的转基因小鼠模型，探讨AQP5通过miR-20a、miR-30a和miR-106b在晶状体发育及成熟过程中的作用，以及对晶状体混浊发生的调控机制，为白内障的治疗提供靶点。

Cataract is the main clinical blinding eye disease with diverse pathogenesis. AQP5 is involved in the maintenance of lens transparency, but the mechanism of action is unclear. There is also no reports of cataracts caused by AQP5 mutations. We found a disease-causing mutation in AQP5 in a hereditary cataract family. In AQP5 knockout mice, the lens was visibly opaque, and the ratio of autophagy markers LC3II/I in lens epithelial cells decreased. The expression of vimentin was increased and aggregated. The expressions of miR-20a, miR-30a and miR-106b, which regulated autophagy, were up-regulated in the miRNAs expression chip of AQP5 knockout mouse lens. It is proposed that AQP5 regulates the autophagy through miR-20a, miR-30a and miR-106b to maintain the transparency of lens. The project will use the lens capsule culture, AQP5 knockout mice, and knock-in mouse models of disease-causing mutations to conduct experiments. Taking autophagy as an entry point, we will explore the role of AQP5 in the development and maturation of lens by regulating miR-20a, miR-30a and miR-106b, and the regulation mechanism of lens opacity, which will provide a target for the treatment of cataract.