Retinal pigment epithelium development, plasticity, and tissue homeostasis

Abstract

The retinal pigment epithelium (RPE) is a simple epithelium interposed between the neural retina and the choroid. Although only 1 cell-layer in thickness, the RPE is a virtual workhorse, acting in several capacities that are essential for visual function and preserving the structural and physiological integrities of neighboring tissues. Defects in RPE function, whether through chronic dysfunction or age-related decline, are associated with retinal degenerative diseases including age-related macular degeneration. As such, investigations are focused on developing techniques to replace RPE through stem cell-based methods, motivated primarily because of the seemingly limited regeneration or self-repair properties of mature RPE. Despite this, RPE cells have an unusual capacity to transdifferentiate into various cell types, with the particular fate choices being highly context-dependent. In this review, we describe recent findings elucidating the mechanisms and steps of RPE development and propose a developmental framework for understanding the apparent contradiction in the capacity for low self-repair versus high transdifferentiation.

Inhibition of the Expression of the Small Heat Shock Protein αB-Crystallin Inhibits Exosome Secretion in Human Retinal Pigment Epithelial Cells in Culture

“…It provides critical physiological support for the maintenance of the photoreceptor neurons (5,6). It is a polarized epithelium, which on its apical side nourishes the neuronal compartment within the eye and on its basal side interacts with the systemic input.…”

Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells

“…The healthy RPE is involved in different functions, ranging from supporting cellular process of retinal photoreceptors, shielding the retina from the light radiation to diurnal phagocytosis of the photoreceptors outer segments (Fuhrmann et al 2014). Up to a few years ago, it was known that RPE was a non-proliferative tissue and, for this reason, incapable to restore itself after damage/pathologies (da Cruz et al 2007).…”

“…The healthy RPE supports cellular processes of retinal photoreceptors, shields the retina from light radiation, provides metabolic support for diurnal phagocytosis of the photoreceptor outer segments and actively maintains the chemical environment and homeostasis of the inner retina (Fuhrmann et al 2014). The formation of drusen (deposits forming between the RPE and an adjacent basement membrane complex known as Bruch's membrane) is the first step of the pathogenesis, leading to the dysfunction and death of RPE cells and, consequently, of the overlying photoreceptor layer.…”

Yap and Taz regulate retinal pigment epithelial cell fate

“…WNT, BMP and TGFβ signaling all control aspects of RPE/NR development through the control of Smads and β-catenin (Sinn and Wittbrodt, 2013;Fuhrmann et al, 2014), both of which have been shown to interact with Yap or Taz (Varelas et al, 2010;Azzolin et al, 2012 (Fossdal et al, 2004;Williamson et al, 2014). SCRA patients carry an autosomal dominant mutation in the Yap-binding domain of TEAD1 and the loss of central RPE in these patients mimics the phenotypes observed in zebrafish yap −/− and Tead1a Y417H overexpression embryos (Fossdal et al, 2004;Jonasson et al, 2007).…”

“…Initially, optic vesicle progenitors express the same transcription factor-encoding genes (such as lhx2, pax6, six3, vsx2 and rx1/2/3), and signaling from surrounding tissues subsequently contributes to the regionalization of the optic vesicle into prospective RPE and NR domains (eye morphogenesis is reviewed in supplementary material Movie 1; Sinn and Wittbrodt, 2013;Fuhrmann et al, 2014). Even after RPE and NR domains are established, both cell populations maintain the ability to transdifferentiate (Sinn and Wittbrodt, 2013;Fuhrmann et al, 2014).…”