Abstract
Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, in recent years, stem cell technologies have offered novel avenues to obtain donor cells for replacement therapies. To date, stem cell–based transplantation in the retina has been attempted as treatment for photoreceptor degeneration, but the same tools could potentially be applied to other retinal cell types, including RGCs. However, RGC-like cells are not an abundant cell type in stem cell–derived cultures and, often, these cells degenerate over time in vitro. To overcome this limitation, we have taken advantage of the neuroprotective properties of Müller glia (one of the main glial cell types in the retina) and we have examined whether Müller glia and the factors they secrete could promote RGC-like cell survival in organoid cultures. Accordingly, stem cell-derived RGC-like cells were co-cultured with adult Müller cells or Müller cell-conditioned media was added to the cultures. Remarkably, RGC-like cell survival was substantially enhanced in both culture conditions, and we also observed a significant increase in their neurite length. Interestingly, Atoh7, a transcription factor required for RGC development, was up-regulated in stem cell-derived organoids exposed to conditioned media, suggesting that Müller cells may also enhance the survival of retinal progenitors and/or postmitotic precursor cells. In conclusion, Müller cells and the factors they release promote organoid-derived RGC-like cell survival, neuritogenesis, and possibly neuronal maturation.
Highlights
Degenerative diseases of the retina are one of the main causes of irreversible vision loss
In an attempt to overcome the decline of stem cell-derived retinal ganglion cells (RGCs)-like cells obtained from pluripotent cells and in light of the neuroprotection afforded to RGCs by Müller cells, in this study we evaluate the effects of co-culturing stem cell-derived
Mouse Embryonic Stem Cells can be Differentiated into RGC-Like Cell Fates
Summary
Degenerative diseases of the retina are one of the main causes of irreversible vision loss. Retinal ganglion cell (RGC) death is the common hallmark of several ocular conditions, including glaucoma, Leber0 s hereditary optic neuropathy (LHON), and other optic neuropathies [1,2,3]. RGC degeneration can lead to vision loss and, glaucoma is one of the leading causes of blindness worldwide [4]. RGC loss is the cornerstone in the management of glaucomatous degenerations, the only FDA-approved treatments are designed to lower intraocular. Cells 2020, 9, 1759 pressure to slow disease progression. These treatments do not reverse RGC damage and fail to reverse vision loss. The drive to develop strategies to functionally replace damaged RGCs has intensified in recent years [5,6,7]
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