Endocytic regulation of RPE cell polarity and adhesion in eye development

Abstract

The retinal pigment epithelium (RPE) is a highly-specialized epithelium, lying in the interface between the neuroretina and the choriocapillaris. This monolayer separates two different environments: photoreceptor layer at the apical side and Bruch’s membrane at the basal side. Therefore, the polarized nature of the RPE is crucial to maintain its functions, including: light absorption and protection against toxic factors, epithelial transport, visual cycle, phagocytosis of shed photoreceptor membranes, and protein secretion. In this study, we examined changes in expression patterns of some well-known epithelial polarity and adhesion markers (Ezrin, $\Beta$ -catenin, F-actin, etc.) in RPE, during the course of mouse eye development, from embryonic to adult stages. We found that, compared to mature RPE, embryonic RPE evidently is not fully polarized. More significantly, when we eliminated “tumour susceptibility gene 101” (TSG101) (one of the key regulators of endo-lysosomal pathway) specifically in the RPE, using conditional knock-out (cKO) models, both in embryonic and adult stages, we found that RPE polarity was severely disturbed. Interestingly, in both cases, retina development of TSG101 cKO was also affected. These results suggest the involvement of endocytosis in regulating RPE cell polarity and adhesion. This will deepen our understanding of the basis of RPE cell polarity, which is required for developing RPE transplants and gene therapy as potential cures for many retinal degenerative diseases (such as Age-related macular degeneration). Future experiments are required to elucidate which proteins are regulated directly by TSG101 and which ones play crucial roles in RPE-retina communication.