Deficiency of Yes-Associated Protein Induces Cataract in Mice.

Cataract is a major cause of blindness worldwide, its complicated and unclear etiopathogenesis limit effective therapy. Here, we found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in lens epithelial cells and Yap conditional knockout (cKO) in the lens leads to cataract. Histologically, Yap deficient lens show fewer epithelial cells, retention of nuclei and accumulation of morgagnian globules in the transitional zone and the posterior area. Mechanistically, GFAP-mediated Yap cKO leads to the reduced proliferation of epithelial cells, delayed fiber cell denucleation and increased cellular senescence in lens. Further RNA profiling analysis reveals Yap cKO results in a significant alteration in gene transcription that is involved in eye development, lens structure, inflammation, cellular proliferation and polarity. Collectively, our data reveal a novel function of Yap in the lens and links Yap deficiency with the development of cataract, making Yap a promising target for cataract therapy.