Deciphering retinal diseases through the generation of three dimensional stem cell-derived organoids: Concise Review

Abstract

Three-dimensional (3D) retinal organoids, in vitro tissue structures derived from self-organizing cultures of differentiating human embryonic stem cells or induced pluripotent stem cells, could recapitulate some aspects of the cytoarchitectural structure and function of the retina in vivo. 3D retinal organoids display huge potential for the investigation of the pathogenesis of monogenic hereditary eye diseases that are related to the malfunction or degeneration of photoreceptors or retinal ganglion cells by providing an effective in vitro tool with multiple applications. In combination with recent genome editing tools, 3D retinal organoids could also represent a reliable and renewable source of transplantable cells for personalized therapies. In this review, we describe the recent advances in human pluripotent stem cells-derived retinal organoids, determination of their histoarchitecture, complexity, and maturity. We also discuss their application as a means to decipher the pathogenesis of retinal diseases, as well as the main drawbacks and challenges. Stem Cells 2019;37:1496-1504.

Keywords: 3D organoids; Disease modeling; Induced pluripotent stem cells; Retinitis pigmentosa.

Figure 1

Schematic overview of current hiPSCs disease 3D retinal modeling. Somatic cells from patients are reprogrammed toward human‐induced pluripotent stem cells (hiPSCs). Derived 3D retinal organoids from hiPSCs serve as a model for further investigation of disease mechanisms, drug, and toxicological screening as well as for future developments of new therapies in patients. The application of gene‐editing technology in patient's hiPSCs could create the gene‐corrected 3D organoids as a cell source for transplantation therapy of hereditary retinal dystrophies. Abbreviations: ACs, amacrine cells; BCs, bipolar cells; GCs, ganglion cells; GCL, ganglion cell layer; HCs, horizontal cells; INL, inner nuclear layer; IPL, inner plexiform layer; IS, inner segment; NFL, nerve fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer; OS, outer segment; PRs, photoreceptors.