Retinal Ganglion Cell Replacement: Current Status and Challenges Ahead

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.

Generation of a Transplantable Population of Human iPSC-Derived Retinal Ganglion Cells

“…Therefore, human pluripotent stem cells (hPSCs) represent one of the most promising sources of human RGCs. Recent development of methods guiding the differentiation of hPSCs toward specific retinal lineages, including RGCs, has emerged as a powerful strategy for disease modeling, drug screening, and gene or cell therapy (Llonch et al, 2018;Rabesandratana et al, 2018;Miltner and La Torre, 2019;Ahmad et al, 2020). Previous studies have demonstrated the ability to differentiate RGCs from plated hPSC-derived embryoid bodies (Riazifar et al, 2014;Sluch et al, 2015;Gill et al, 2016;Teotia et al, 2017).…”

Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells

“…We hypothesized that RGCs may also have the immunosuppressive properties such as RPEs. Degeneration and apoptosis of RGCs that occur in glaucoma and optic neuropathy can cause irreversible visual impairment [11][12][13][14]. In particular, glaucoma is a type of progressive degeneration of RGCs that is estimated to affect more than 70 million people worldwide and is the leading cause of irreversible blindness [12,15,16].…”

Structural engraftment and topographic spacing of transplanted human stem cell-derived retinal ganglion cells

“…[35][36][37][38] Some have speculated that the ILM could impede retinal integration of various cell types following intravitreal transplantation. [39][40][41][42][43] We directly evaluated ILM's impact on intraretinal migration of mesenchymal stem cells (MSCs) specifically and showed that reactive gliosis, not the ILM, impedes engraftment. 44 However, the role of the ILM in engraftment of transplanted neurons, including RGCs, has not been directly investigated.…”