GBD 2019 Blindness and Vision Impairment Collaborators. Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study. Lancet Glob. Health 9, e130–e143 (2021).
Rein, D. B. et al. The economic burden of vision loss and blindness in the United States. Ophthalmology 129, 369–378 (2021).
Age-Related Eye Disease Study Research et al. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch. Ophthalmol. 125, 1225–1232 (2007).
Google Scholar
Caras, I. W., Collins, L. R. & Creasey, A. A. A stem cell journey in ophthalmology: from the bench to the clinic. Stem Cells Transl. Med. 10, 1581–1587 (2021).
Google Scholar
Haruta, M. et al. In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest. Ophthalmol. Vis. Sci. 45, 1020–1025 (2004).
Google Scholar
Idelson, M. et al. Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5, 396–408 (2009).
Google Scholar
Osakada, F., Ikeda, H., Sasai, Y. & Takahashi, M. Stepwise differentiation of pluripotent stem cells into retinal cells. Nat. Protoc. 4, 811–824 (2009).
Google Scholar
Luo, J. et al. Human retinal progenitor cell transplantation preserves vision. J. Biol. Chem. 289, 6362–6371 (2014).
Google Scholar
Carr, A. J. et al. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS ONE 4, e8152 (2009).
Google Scholar
Schwartz, S. D. et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet 385, 509–516 (2015).
Google Scholar
Mehat, M. S. et al. Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells in macular degeneration. Ophthalmology 125, 1765–1775 (2018).
Google Scholar
Sharma, R. et al. Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. Sci. Transl. Med. 11, eaaw7624 (2019).
Google Scholar
Chirco, K. R. et al. Preparation and evaluation of human choroid extracellular matrix scaffolds for the study of cell replacement strategies. Acta Biomater. 57, 293–303 (2017).
Google Scholar
Koss, M. J. et al. Subretinal implantation of a monolayer of human embryonic stem cell-derived retinal pigment epithelium: a feasibility and safety study in Yucatan minipigs. Graefes Arch. Clin. Exp. Ophthalmol. 254, 1553–1565 (2016).
Google Scholar
Kashani, A. H. et al. One-year follow-up in a phase 1/2a clinical trial of an allogeneic RPE cell bioengineered implant for advanced dry age-related macular degeneration. Transl. Vis. Sci. Technol. 10, 13 (2021).
Google Scholar
Lingam, S. et al. cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates. Stem Cell Res. Ther. 12, 464 (2021).
Google Scholar
Shirai, H. et al. Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration. Proc. Natl Acad. Sci. USA 113, E81–E90 (2016).
Google Scholar
Chao, J. R. et al. Transplantation of human embryonic stem cell-derived retinal cells into the subretinal space of a non-human primate. Transl. Vis. Sci. Technol. 6, 4 (2017).
Google Scholar
Kupperman, B. D. et al. ARVO annual meeting abstract: Safety and activity of a single, intravitreal injection of human retinal progenitor cells (JCell) for treatment of retinitis pigmentosa (RP). Invest Ophthal Vis Sci. 59, 2987 (2018).
Lin, B., McLelland, B. T., Mathur, A., Aramant, R. B. & Seiler, M. J. Sheets of human retinal progenitor transplants improve vision in rats with severe retinal degeneration. Exp. Eye Res. 174, 13–28 (2018).
Google Scholar
Nakano, T. et al. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10, 771–785 (2012).
Google Scholar
Capowski, E. E. et al. Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines. Development 146, dev171686 (2019).
Google Scholar
Zhong, X. et al. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nat. Commun. 5, 4047 (2014).
Google Scholar
Ribeiro, J. et al. Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors. Cell Rep. 35, 109022 (2021).
Google Scholar
Aboualizadeh, E. et al. Imaging transplanted photoreceptors in living nonhuman primates with single-cell resolution. Stem Cell Rep. 15, 482–497 (2020).
Google Scholar
Morgan, J. & Wong, R. Development of cell types and synaptic connections in the retina. in Webvision: The Organization of the Retina and Visual System (eds. Kolb, H., Fernandez, E. & Nelson, R.) (University of Utah Health Sciences, 1995).
Marc, R. E., Jones, B. W., Watt, C. B. & Strettoi, E. Neural remodeling in retinal degeneration. Prog. Retin. Eye Res. 22, 607–655 (2003).
Google Scholar
Sekirnjak, C. et al. Changes in physiological properties of rat ganglion cells during retinal degeneration. J. Neurophysiol. 105, 2560–2571 (2011).
Google Scholar
Shekhar, K. et al. Comprehensive classification of retinal bipolar neurons by single-cell transcriptomics. Cell 166, 1308–1323.e1330 (2016).
Google Scholar
Gabriel, E. et al. Human brain organoids assemble functionally integrated bilateral optic vesicles. Cell Stem Cell 28, 1740–1757 e1748 (2021).
Google Scholar
Miltner, A. M. & La Torre, A. Retinal ganglion cell replacement: current status and challenges ahead. Dev. Dyn. 248, 118–128 (2019).
Google Scholar
Xiao, D. et al. In vivo regeneration of ganglion cells for vision restoration in mammalian retinas. Front. Cell Dev. Biol. 9, 755544 (2021).
Google Scholar
Peng, Y. R. et al. Molecular classification and comparative taxonomics of foveal and peripheral cells in primate retina. Cell 176, 1222–1237 (2019).
Google Scholar
Venugopalan, P. et al. Transplanted neurons integrate into adult retinas and respond to light. Nat. Commun. 7, 10472 (2016).
Google Scholar
Wu, Y. R. et al. Transplanted mouse embryonic stem cell-derived retinal ganglion cells integrate and form synapses in a retinal ganglion cell-depleted mouse model. Invest. Ophthalmol. Vis. Sci. 62, 26 (2021).
Google Scholar
Lahne, M., Nagashima, M., Hyde, D. R. & Hitchcock, P. F. Reprogramming Müller glia to regenerate retinal neurons. Annu Rev. Vis. Sci. 6, 171–193 (2020).
Google Scholar
Dyer, M. A. & Cepko, C. L. Control of Muller glial cell proliferation and activation following retinal injury. Nat. Neurosci. 3, 873–880 (2000).
Google Scholar
Hoang, T. et al. Gene regulatory networks controlling vertebrate retinal regeneration. Science 370, eabb8598 (2020).
Google Scholar
Jorstad, N. L. et al. Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature 548, 103–107 (2017).
Google Scholar
Livesey, F. J. & Cepko, C. L. Vertebrate neural cell-fate determination: lessons from the retina. Nat. Rev. Neurosci. 2, 109–118 (2001).
Google Scholar
Jorstad, N. L. et al. Stimulation of functional neuronal regeneration from Muller glia in adult mice. Nature 548, 103–107 (2017).
Google Scholar
Todd, L. et al. Efficient stimulation of retinal regeneration from Muller glia in adult mice using combinations of proneural bHLH transcription factors. Cell Rep. 37, 109857 (2021).
Google Scholar
Scholler, J. et al. Dynamic full-field optical coherence tomography: 3D live-imaging of retinal organoids. Light Sci. Appl. 9, 140 (2020).
Google Scholar
Rossi, E. A. et al. Imaging individual neurons in the retinal ganglion cell layer of the living eye. Proc. Natl Acad. Sci. USA 114, 586–591 (2017).
Google Scholar
Liu, Z. et al. Quantification of retinal ganglion cell morphology in human glaucomatous eyes. Invest. Ophthalmol. Vis. Sci. 62, 34 (2021).
Google Scholar
Palczewska, G. et al. Two-photon imaging of the mammalian retina with ultrafast pulsing laser. JCI Insight 3, e121555 (2018).
Google Scholar
Pandiyan, V. P. et al. The optoretinogram reveals the primary steps of phototransduction in the living human eye. Sci. Adv. 6, eabc1124 (2020).
Google Scholar
Ahuja, A. K. et al. Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. Br. J. Ophthalmol. 95, 539–543 (2011).
Google Scholar
Dagnelie, G. et al. Performance of real-world functional vision tasks by blind subjects improves after implantation with the Argus(R) II retinal prosthesis system. Clin. Exp. Ophthalmol. 45, 152–159 (2017).
Google Scholar
Nanduri, D. et al. Frequency and amplitude modulation have different effects on the percepts elicited by retinal stimulation. Invest. Ophthalmol. Vis. Sci. 53, 205–214 (2012).
Google Scholar
Stingl, K. et al. Interim results of a multicenter trial with the new electronic subretinal implant alpha AMS in 15 patients blind from inherited retinal degenerations. Front. Neurosci. 11, 445 (2017).
Google Scholar
Ayton, L. N. et al. An update on retinal prostheses. Clin. Neurophysiol. 131, 1383–1398 (2020).
Google Scholar
Lorach, H. et al. Photovoltaic restoration of sight with high visual acuity. Nat. Med. 21, 476–482 (2015).
Google Scholar
Palanker, D., Le Mer, Y., Mohand-Said, S., Muqit, M. & Sahel, J. A. Photovoltaic restoration of central vision in atrophic age-related macular degeneration. Ophthalmology 127, 1097–1104 (2020).
Google Scholar
Maguire, A. M. et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology 126, 1273–1285 (2019).
Google Scholar
Russell, S. et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet 390, 849–860 (2017).
Google Scholar
Cideciyan, A. V. et al. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc. Natl Acad. Sci. USA 110, E517–E525 (2013).
Google Scholar
Bucher, K., Rodriguez-Bocanegra, E., Dauletbekov, D. & Fischer, M. D. Immune responses to retinal gene therapy using adeno-associated viral vectors — implications for treatment success and safety. Prog. Retin. Eye Res. 83, 100915 (2021).
Google Scholar
Van Gelder, R. N. Gene therapy approaches to slow or reverse blindness from inherited retinal degeneration: growth factors and optogenetics. Int. Ophthalmol. Clin. 61, 209–228 (2021).
Google Scholar
Kauper, K. et al. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest. Ophthalmol. Vis. Sci. 53, 7484–7491 (2012).
Google Scholar
Chew, E. Y. et al. Effect of ciliary neurotrophic factor on retinal neurodegeneration in patients with macular telangiectasia type 2: a randomized clinical trial. Ophthalmology 126, 540–549 (2019).
Google Scholar
Sahel, J. A. et al. Partial recovery of visual function in a blind patient after optogenetic therapy. Nat. Med. 27, 1223–1229 (2021).
Google Scholar
Berry, M. H. et al. Restoration of high-sensitivity and adapting vision with a cone opsin. Nat. Commun. 10, 1221 (2019).
Google Scholar
Polosukhina, A. et al. Photochemical restoration of visual responses in blind mice. Neuron 75, 271–282 (2012).
Google Scholar
Tochitsky, I. et al. Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells. Neuron 81, 800–813 (2014).
Google Scholar
Tochitsky, I. et al. How azobenzene photoswitches restore visual responses to the blind retina. Neuron 92, 100–113 (2016).
Google Scholar
Koga, K., Wang, B. & Kaneko, S. Current and furutre perspectives of HLA-edited induced pluripotent stem cells. Inflamm. Regen. 40, 223 (2020).
Google Scholar
Liu, Y. & Lee, R. K. Cell transplantation to replace retinal ganglion cells faces challenges — the Switchboard Dilemma. Neural Regen. Res 16, 1138–1143 (2021).
Google Scholar
Fligor, C. M. et al. Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids. Stem Cell Rep. 16, 2228–2241 (2021).
Google Scholar
Yungher, B. J., Ribeiro, M. & Park, K. K. Regenerative responses and axon pathfinding of retinal ganglion cells in chronically injured mice. Invest. Ophthalmol. Vis. Sci. 58, 1743–1750 (2017).
Google Scholar
De Lima, S., Koriyama, Y., Kurimoto, T. & Benowitz, L. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc. Natl Acad. Sci. USA 109, 9149–9154 (2012).
Google Scholar
Glennon, E., Svirsky, M. A. & Froemke, R. C. Auditory cortical plasticity in cochlear implant users. Curr. Opin. Neurobiol. 60, 108–114 (2020).
Google Scholar
Palanker, D., Le Mer, Y., Mohand-Said, S. & Sahel, J. A. Simultaneous perception of prosthetic and natural vision in AMD patients. Nat. Commun. 13, 513 (2022).
Google Scholar
Schwartz, S. D. et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379, 713–720 (2012).
Google Scholar
Petoe, M. A. et al. A second-generation (44-channel) suprachoroidal retinal prosthesis: interim clinical trial results. Transl. Vis. Sci. Technol. 10, 12 (2021).
Google Scholar
Morgan, J. L., Dhingra, A., Vardi, N. & Wong, R. O. L. Axons and dendrites originate from neuroepithelial-like processes of retinal bipolar neurons. Nat. Neurosci. 9, 85–92 (2006).
Google Scholar