Recent Achievements in the Heterogeneity of Mammalian and Human Retinal Pigment Epithelium: In Search of a Stem Cell

Abstract

Retinal pigment epithelium (RPE) cells are important fundamentally for the development and function of the retina. In this regard, the study of the morphological and molecular properties of RPE cells, as well as their regenerative capabilities, is of particular importance for biomedicine. However, these studies are complicated by the fact that, despite the external morphological similarity of RPE cells, the RPE is a population of heterogeneous cells, the molecular genetic properties of which have begun to be revealed by sequencing methods only in recent years. This review carries out an analysis of the data from morphological and molecular genetic studies of the heterogeneity of RPE cells in mammals and humans, which reveals the individual differences in the subpopulations of RPE cells and the possible specificity of their functions. Particular attention is paid to discussing the properties of "stemness," proliferation, and plasticity in the RPE, which may be useful for uncovering the mechanisms of retinal diseases associated with pathologies of the RPE and finding new ways of treating them.

Keywords: RPE; RPE stem cells (RPESCs); cell subpopulation; heterogeneity; morphometry map; reprogramming; retinal pigment epithelium.

Figure 1

Schematic representation of a heat map of the retinal pigment epithelium (RPE), and a diagram of the distribution of photoreceptors of the human retina: (a) concentric zones of the adult human eye RPE: P1—fovea and parafovea; P2—perifovea; P3—the immediate periphery (or equatorial region); P4—a ring of RPE cells identified for the first time, resembling the RPE cells of zone P2; and P5—the far periphery, ending with the ora serrata; the dark blue staining indicates small hexagonal RPE cells of regular shape; a decrease in the blue color saturation with a transition to yellow indicates that the cell area of the RPE increases, cell hexagonality is disrupted, cells become more elongated, and cell density decreases in the monolayer; (b) the concentric zones of M and L cone distribution in the adult retina; (c) the concentric zones of S cone distribution in the adult retina; and (d) the concentric zones of rod distribution in the adult retina. Interpretation has been conducted in accordance with [1] and [38]. The more saturated the color, the higher the cell density. RPE—retinal pigment epithelium; L/M—Long wavelength/Medium wavelength cones; and S—Short wavelength cones.