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Regenerative and restorative medicine for eye disease

Abstract

Causes of blindness differ across the globe; in higher-income countries, most blindness results from the degeneration of specific classes of cells in the retina, including retinal pigment epithelium (RPE), photoreceptors, and retinal ganglion cells. Advances over the past decade in retinal regenerative medicine have allowed each of these cell types to be produced ex vivo from progenitor stem cells. Here, we review progress in applying these technologies to cell replacement — with the goal of vision restoration in degenerative disease. We discuss the landscape of human clinical trials for RPE transplantation and advanced preclinical studies for other cell types. We also review progress toward in situ repair of retinal degeneration using endogenous progenitor cells. Finally, we provide a high-level overview of progress toward prosthetic ocular vision restoration, including advanced photovoltaic devices, opsin-based gene therapy, and small-molecule photoswitches. Progress in each of these domains is at or near the human clinical-trial stage, bringing the audacious goal of vision restoration within sight.

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Fig. 1: Visual pathways and approaches to vision restoration.
Fig. 2: Cell sources for replacement therapies.

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Acknowledgements

Special thanks to P. Sieving for conceptualizing the Audacious Goals Initiative and pushing the field of regenerative medicine in the eye forward. Thanks also to S. Becker for shepherding the vision of AGI and its progress. R.N.V.G. acknowledges support of an unrestricted grant from Research to Prevent Blindness and the Mark Daly, MD Research Fund.

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Correspondence to Russell N. Van Gelder.

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R.N.V.G., R.O.W., M.F.C., C.N.S., M.A.D. and T.N.G. have no competing interests. L.A.L. serves as paid consultant to Pirlenia, Janssen, Roche, Neuoptika, Quark, Perfuse, Genentech, Regenera, Unity, Eyevensys, Santen and Aerie.

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Nature Medicine thanks Daniel Palanker and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary handling editor: Karen O’Leary, in collaboration with the Nature Medicine team.

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Van Gelder, R.N., Chiang, M.F., Dyer, M.A. et al. Regenerative and restorative medicine for eye disease. Nat Med 28, 1149–1156 (2022). https://doi.org/10.1038/s41591-022-01862-8

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