The proliferation, differentiation and homeostasis of lens anterior monolayer epithelium determine the lens growth, size, shape and transparency, which are absolutely required for focusing and transmitting a light image onto the retina. The goal of this proposal is to test a novel hypothesis that the intrinsic heterogeneity of lens epithelial cells regulates lens growth and homeostasis, and distinctive cell clusters of lens monolayer epithelium are precisely organized for mediating external signals of surrounding ocular tissues and environmental stimuli to regulate the lens growth, size, shape and transparency, and that disruptions of specific cell cluster(s) impair the regulation of lens growth and homeostasis to lead to various lens and/or eye pathological outcomes including cataracts, microphthalmia, and macrophthalmia.
This study aims to investigate the molecular and cellular bases of the heterogeneity of lens epithelium that consists of distinct cell clusters with different functions. Moreover, we will explore novel regulatory mechanisms of distinct epithelial cell clusters in lens growth control, lens homeostasis maintenance and various lens pathological outcomes. We will gain insights into fundamental mechanisms about how distinct epithelial cell clusters selectively response to various external stimuli to regulate the lens size and homeostasis over the course of postnatal lens development and aging.