Can Ganglion Cells Be Repaired Before That Dissapear

Review

. 2019 Jan;248(1):118-128.

doi: 10.1002/dvdy.24672. Epub 2018 Oct 11.

Retinal Ganglion Cell Replacement: Current Status and Challenges Ahead

Affiliations

PMID: 30242792
PMCID: PMC7141838
DOI: 10.1002/dvdy.24672

Free PMC article

Review

Retinal Ganglion Cell Replacement: Current Status and Challenges Ahead

Adam M Miltner et al. Dev Dyn. 2019 Jan .

Free PMC article

Abstract

The neurons of the retina can be affected by a wide variety of inherited or environmental degenerations that can lead to vision loss and even blindness. Retinal ganglion cell (RGC) degeneration is the hallmark of glaucoma and other optic neuropathies that affect millions of people worldwide. Numerous strategies are being trialed to replace lost neurons in different degeneration models, and in recent years, stem cell technologies have opened promising avenues to obtain donor cells for retinal repair. Stem cell-based transplantation has been most frequently used for the replacement of rod photoreceptors, but the same tools could potentially be used for other retinal cell types, including RGCs. However, RGCs are not abundant in stem cell-derived cultures, and in contrast to the short-distance wiring of photoreceptors, RGC axons take a long and intricate journey to connect with numerous brain nuclei. Hence, a number of challenges still remain, such as the ability to scale up the production of RGCs and a reliable and functional integration into the adult diseased retina upon transplantation. In this review, we discuss the recent advancements in the development of replacement therapies for RGC degenerations and the challenges that we need to overcome before these technologies can be applied to the clinic. Developmental Dynamics 248:118-128, 2019. © 2018 Wiley Periodicals, Inc.

Keywords: Retinal ganglion cells; cell replacement; retinal organoids; stem cells.

Figures

**Figure 1.**
Cytoarchitecture of the mammalian retina. A) The retina is organized in three main layers, the outer nuclear layer (ONL), the inner nuclear layer (INL) and the ganglion cell layer (GCL), and contains six main neuronal cell types, the cone and rod photoreceptors (light and dark green, respectively), the horizontal cells (blue), the bipolar cells (orange), the amacrine cells (light blue), and the retinal ganglion cells (red). B) All RGCs (red) send their axons to the center of the eye, a region called the optic nerve head (ONH). The image shows the RGCs of an adult flat-mounted retina. C) As axons leave the eye, they bundle to form the optic nerve (ON). The image shows a section of a E13.5 mouse retina immunolabeled with Tuj1 (red) and co-stained with DAPI (blue).

**Figure 2.**
Upon differentiation, undifferentiated pluripotent stem cells (A) can be directed towards retinal cell fates following several steps that resemble normal developmental stages. First, they develop into a neural epithelium (B) that evaginates to form optic vesicle-like structures (arrows in C), and finally optic cup-like structures (arrows in D). The retinal progenitors can then differentiate into RGCs (E). The arrows in E show fluorescently-labeled RGCs (green) in a 10-day retinal organoid. Abbreviations: OV: optic vesicles, OC: optic cups, RGC: Retinal Ganglion Cells. Scale: 100 microns

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