Format

Send to

Choose Destination
Aging Dis. 2019 Apr 1;10(2):293-306. doi: 10.14336/AD.2018.0910. eCollection 2019 Apr.

Deficiency of Yes-Associated Protein Induces Cataract in Mice.

He Q1,2,3, Gao Y1,2,3, Wang T4,5, Zhou L2,3, Zhou W4,5, Yuan Z2.

Author information

1
1State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
2
2The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
3
3College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
4
4Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
5
5State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.

Abstract

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.

KEYWORDS:

Yap; cataract; cell proliferation; cell senescence; lens epithelial cells

Conflict of interest statement

Conflict of interests The authors have no conflicts of interest related to this work to declare.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center