Sohocki, M. M. et al. Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum. Mutat. 17, 42–51 (2001).
Google Scholar
Liew, G., Michaelides, M. & Bunce, C. A comparison of the causes of blindness certifications in England and Wales in working age adults (16–64 years), 1999–2000 with 2009–2010. BMJ Open. 4, e004015 (2014).
Google Scholar
Wong, W. L. et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob. Health 2, e106–e116 (2014).
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
Xue, K. et al. Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia. Nat. Med. 24, 1507–1512 (2018).
Google Scholar
Cukras, C. et al. Retinal AAV8-RS1 gene therapy for X-linked retinoschisis: initial findings from a phase I/IIa trial by intravitreal delivery. Mol. Ther. 26, 2282–2294 (2018).
Google Scholar
Cehajic-Kapetanovic, J. et al. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat. Med. 26, 354–359 (2020).
Google Scholar
Kantor, A. et al. CRISPR genome engineering for retinal diseases. Prog. Mol. Biol. Transl. Sci. 182, 29–79 (2021).
Google Scholar
Quinn, J. et al. Genome-editing strategies for treating human retinal degenerations. Hum. Gene Ther. 32, 247–259 (2021).
Google Scholar
Maeder, M. L. et al. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nat. Med. 25, 229–233 (2019).
Google Scholar
Jonas, J. B. et al. Glaucoma. Lancet 390, 2183–2193 (2017).
Google Scholar
Guy, J. et al. Gene therapy for Leber hereditary optic neuropathy: low- and medium-dose visual results. Ophthalmology 124, 1621–1634 (2017).
Google Scholar
Vignal, C. et al. Safety of rAAV2/2-ND4 gene therapy for Leber hereditary optic neuropathy. Ophthalmology 125, 945–947 (2018).
Google Scholar
Wu, S., Chang, K. C., Nahmou, M. & Goldberg, J. L. Induced pluripotent stem cells promote retinal ganglion cell survival after transplant. Invest. Ophthalmol. Vis. Sci. 59, 1571–1576 (2018).
Google Scholar
Zhang, X. et al. Cell transplantation of retinal ganglion cells derived from hESCs. Restor. Neurol. Neurosci. 38, 131–140 (2020).
Google Scholar
Suen, H. C. et al. Transplantation of retinal ganglion cells derived from male germline stem cell as a potential treatment to glaucoma. Stem Cells Dev. 28, 1365–1375 (2019).
Google Scholar
Jones, B. W. et al. Retinal remodeling triggered by photoreceptor degenerations. J. Comp. Neurol. 464, 1–16 (2003).
Google Scholar
Marc, R. E. & Jones, B. W. Retinal remodeling in inherited photoreceptor degenerations. Mol. Neurobiol. 28, 139–147 (2003).
Google Scholar
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
Jones, B. W. & Marc, R. E. Retinal remodeling during retinal degeneration. Exp. Eye Res. 81, 123–137 (2005).
Google Scholar
Marc, R. E. et al. Neural reprogramming in retinal degeneration. Invest. Ophthalmol. Vis. Sci. 48, 3364–3371 (2007).
Google Scholar
Cuenca, N. et al. Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases. Prog. Retin. Eye Res. 43, 17–75 (2014).
Google Scholar
Jones, B. W. et al. Retinal remodeling in human retinitis pigmentosa. Exp. Eye Res. 150, 149–165 (2016).
Google Scholar
Krishnamoorthy, V. et al. Retinal remodeling: concerns, emerging remedies and future prospects. Front. Cell Neurosci. 10, 38 (2016).
Google Scholar
Pfeiffer, R. L., Marc, R. E. & Jones, B. W. Persistent remodeling and neurodegeneration in late-stage retinal degeneration. Prog. Retin. Eye Res. 74, 100771 (2019).
Google Scholar
Eleftheriou, C. G. et al. Meclofenamic acid improves the signal to noise ratio for visual responses produced by ectopic expression of human rod opsin. Mol. Vis. 23, 334–345 (2017).
Google Scholar
Telias, M. et al. Retinoic acid induces hyperactivity, and blocking its receptor unmasks light responses and augments vision in retinal degeneration. Neuron 102, 574–586.e5 (2019).
Google Scholar
Acland, G. M. et al. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28, 92–95 (2001).
Google Scholar
Bainbridge, J. W. B. et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N. Engl. J. Med. 358, 2231–2239 (2008).
Google Scholar
Maguire, A. M. et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N. Engl. J. Med. 358, 2240–2248 (2008).
Google Scholar
Cideciyan, A. V. et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc. Natl Acad. Sci. USA 105, 15112–15117 (2008).
Google Scholar
Fischer, M. D. et al. Safety and vision outcomes of subretinal gene therapy targeting cone photoreceptors in achromatopsia: a nonrandomized controlled trial. JAMA Ophthalmol. 138, 643–651 (2020).
Google Scholar
Josan, A. S. et al. Microperimetry Hill of vision and volumetric measures of retinal sensitivity. Transl. Vis. Sci. Technol. 10, 12 (2021).
Google Scholar
MacDonald, I. M. et al. Perspectives on gene therapy: choroideremia represents a challenging model for the treatment of other inherited retinal degenerations. Trans. Vis. Sci. Tech. 9, 17 (2020).
McClements, M. E. et al. An AAV dual vector strategy ameliorates the Stargardt phenotype in adult Abca4-/- mice. Hum. Gene Ther. 30, 590–600 (2019).
Google Scholar
Hirsch, M. L., Wolf, S. J. & Samulski, R. J. Delivering transgenic DNA exceeding the carrying capacity of AAV vectors. Methods Mol. Biol. 1382, 21–39 (2016).
Google Scholar
Trapani, I. et al. Improved dual AAV vectors with reduced expression of truncated proteins are safe and effective in the retina of a mouse model of Stargardt disease. Hum. Mol. Genet. 24, 6811–6825 (2015).
Google Scholar
T Trapani, I. et al. Effective delivery of large genes to the retina by dual AAV vectors. EMBO Mol. Med. 6, 194–211 (2014).
Yi-Ting, T. et al. Clustered regularly interspaced short palindromic repeats-based genome surgery for the treatment of autosomal dominant retinitis pigmentosa. Ophthalmology 125, 1421–1430 (2018).
Diakatou, M., Manes, G., Bocquet, B., Meunier, I. & Kalatzis, V. Genome editing as a treatment for the most prevalent causative genes of autosomal dominant retinitis pigmentosa. Int. J. Mol. Sci. 20, 2542 (2019).
Google Scholar
Sternberg, S. H., Redding, S., Jinek, M., Greene, E. C. & Doudna, J. A. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature 507, 62–67 (2014).
Google Scholar
Sander, J. D. & Joung, J. K. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol. 32, 347–355 (2014).
Google Scholar
Cai, Y. et al. In vivo genome editing rescues photoreceptor degeneration via a Cas9/RecA-mediated homology-directed repair pathway. Sci. Adv. 5, eaav3335 (2019).
Google Scholar
Bakondi, B. et al. In vivo CRISPR/Cas9 Gene editing corrects retinal dystrophy in the S334ter-3 rat model of autosomal dominant retinitis pigmentosa. Mol. Ther. 24, 556–563 (2016).
Google Scholar
Tsai, Y. et al. CRISPR-based genome surgery for the treatment of autosomal dominant retinitis. Ophthalmology 125, 1421–1430 (2018).
Google Scholar
McClements, M. E., Staurenghi, F., MacLaren, R. E. & Cehajic-Kapetanovic, J. Optogenetic gene therapy for the degenerate retina: recent advances. Front. Neurosci. 11, 570909 (2020).
Bi, A. et al. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50, 23–33 (2006).
Google Scholar
Zhang, Y., Ivanova, E., Bi, A. & Pan, Z. H. Ectopic expression of multiple microbial rhodopsins restores ON and OFF light responses in retinas with photoreceptor degeneration. J. Neurosci. 29, 9186–9196 (2009).
Google Scholar
Thyagarajan, S. et al. Visual function in mice with photoreceptor degeneration and transgenic expression of channelrhodopsin 2 in ganglion cells. J. Neurosci. 30, 8745–8758 (2010).
Google Scholar
Doroudchi, M. M. et al. Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness. Mol. Ther. 19, 1220–1229 (2011).
Google Scholar
Sengupta, A. et al. Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina. EMBO Mol. Med. 8, 1248–1264 (2016).
Google Scholar
Lagali, P. S. et al. Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat. Neurosci. 11, 667–675 (2008).
Google Scholar
Macé, E. et al. Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV restores ON and OFF visual responses in blind mice. Mol. Ther. 23, 7–16 (2015).
Google Scholar
Busskamp, V. et al. Genetic rectivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329, 413–417 (2010).
Google Scholar
Gauvain, G. et al. Optogenetic therapy: high spatiotemporal resolution and pattern discrimination compatible with vision restoration in non-human primates. Commun. Biol. 4, 125 (2021).
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
Cehajic-Kapetanovic, J. et al. Restoration of vision with ectopic expression of human rod opsin. Curr. Biol. 25, 2111–2122 (2015).
Google Scholar
Gaub, B. M., Berry, M. H., Holt, A. E., Isacoff, E. Y. & Flannery, J. G. Optogenetic vision restoration using rhodopsin for enhanced sensitivity. Mol. Ther. 23, 1562–1571 (2015).
Google Scholar
Lin, B., Koizumi, A., Tanaka, N., Panda, S. & Masland, R. H. Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc. Natl Acad. Sci. USA 105, 16009–16014 (2008).
Google Scholar
De Silva, S. R. et al. Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy. Proc. Natl Acad. Sci. USA 114, 11211–11216 (2017).
Google Scholar
van Wyk, M., Pielecka-Fortuna, J., Löwel, S. & Kleinlogel, S. Restoring the ON switch in blind retinas: opto-mGluR6, a next-generation, cell-tailored optogenetic tool. PLoS Biol. 13, e1002143 (2015).
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
Gaub, B. M. et al. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells. Proc. Natl Acad. Sci. USA 111, E5574–E5583 (2014).
Google Scholar
Berry, M. H. et al. Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor. Nat. Commun. 8, 1862 (2017).
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., Trautman, J., Gallerani, N., Malis, J. G. & Kramer, R. H. Restoring visual function to the blind retina with a potent, safe and long-lasting photoswitch. Sci. Rep. 7, 45487 (2017).
Google Scholar
Cehajic-Kapetanovic, J. et al. Glycosidic enzymes enhance retinal transduction following intravitreal delivery of AAV2. Mol. Vis. 17, 1771–1783 (2011).
Google Scholar
Cehajic-Kapetanovic, J., Milosavljevic, N., Bedford, R. A., Lucas, R. J. & Bishop, P. N. Efficacy and safety of glycosidic enzymes for improved gene delivery to the retina following intravitreal injection in mice. Mol. Ther. Methods Clin. Dev. 9, 192–202 (2017).
Google Scholar
Fick, A. ‘On liquid diffusion’. Ann. Phys. Chem. 94, 59 (1855).
Dalkara, D. et al. In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous. Sci. Transl. Med. 5, 189ra76 (2013).
Google Scholar
Kotterman, M. A. et al. Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates. Gene Ther. 22, 116–126 (2015).
Google Scholar
Cehajic-Kapetanovic, J. et al. Highest reported visual acuity after electronic retinal implantation. Acta Ophthalmol. 98, 736–740 (2020).
Google Scholar
McClements, M. E. et al. AAV induced expression of human rod and cone opsin in bipolar cells of a mouse model of retinal degeneration, BioMed. Res. Int. https://doi.org/10.1155/2021/4014797 (2021).
Thanos, C. G. et al. Sustained secretion of ciliary neurotrophic factor to the vitreous, using the encapsulated cell therapy-based NT-501 intraocular device. Tissue Eng. 10, 1617–1622 (2004).
Google Scholar
Lund, R. D. et al. Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. Stem Cells 25, 602–611 (2007).
Google Scholar
Ho, A. C. et al. Experience with a subretinal cell-based therapy in patients with geographic atrophy secondary to age-related macular degeneration. Am. J. Ophthalmol. 179, 67–80 (2017).
Google Scholar
Park, S. S. Cell therapy applications for retinal vascular diseases: diabetic retinopathy and retinal vein occlusion. Invest. Ophthalmol. Vis. Sci. 57, ORSFj1–ORSFj10 (2016).
Google Scholar
Park, S. S. et al. Intravitreal autologous bone marrow CD34+ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings. Invest. Ophthalmol. Vis. Sci. 56, 81–89 (2014).
Google Scholar
Otani, A. et al. Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J. Clin. Invest. 114, 765–774 (2004).
Google Scholar
Koh, S. et al. Subretinal human umbilical tissue-derived cell transplantation preserves retinal synaptic connectivity and attenuates Müller glial reactivity. J. Neurosci. 38, 2923–2943 (2018).
Google Scholar
Koh, S. et al. Human umbilical tissue-derived cells promote synapse formation and neurite outgrowth via thrombospondin family proteins. J. Neurosci. 35, 15649–15665 (2015).
Google Scholar
Börger, V. et al. Mesenchymal stem/stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents. Int. J. Mol. Sci. 18, 1450 (2017).
Google Scholar
Zhou, J. et al. Retinal progenitor cells release extracellular vesicles containing developmental transcription factors, microRNA and membrane proteins. Sci. Rep. 8, 2823 (2018).
Google Scholar
Knickelbein, J. E. et al. Modulation of immune responses by extracellular vesicles from retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 57, 4101–4107 (2016).
Google Scholar
Kashani, A. H. et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration. Sci. Transl. Med. 10, eaao4097 (2018).
Google Scholar
Mandai, M. et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 376, 1038–1046 (2017).
Google Scholar
da Cruz, L. et al. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat. Biotechnol. 36, 328–337 (2018).
Google Scholar
Schwartz, S. D. et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379, 713–720 (2012).
Google Scholar
Schwartz, S. D., Tan, G., Hosseini, H. & Nagiel, A. Subretinal transplantation of embryonic stem cell–derived retinal pigment epithelium for the treatment of macular degeneration: an assessment at 4 years. Invest. Ophthalmol. Vis. Sci. 57, ORSFc1–ORSFc9 (2016).
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, eaat5580 (2019).
Google Scholar
Ben M’Barek, K. et al. Human ESC–derived retinal epithelial cell sheets potentiate rescue of photoreceptor cell loss in rats with retinal degeneration. Sci. Transl. Med. 9, eaai7471 (2019).
Kuppermann, B. D., Boyer, D. S., Mills, B., Yang, J. & Klassen, H. J. Safety and activity of a single, intravitreal injection of human retinal progenitor cells (jCell) for treatment of retinitis pigmentosa (RP). Invest. Ophthalmol. Vis. Sci. 59, 2987 (2018).
Yang, J. et al. Translational development of human retinal progenitor cells for treatment of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 54, 2237 (2013).
Warfvinge, K. et al. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs. J. Transplant. 2011, 948740 (2011).
Google Scholar
Aftab, U. et al. Growth kinetics and transplantation of human retinal progenitor cells. Exp. Eye Res. 89, 301–310 (2009).
Google Scholar
Redenti, S. et al. Retinal tissue engineering using mouse retinal progenitor cells and a novel biodegradable, thin-film poly(e-caprolactone) nanowire scaffold. J. Ocul. Biol. Dis. Infor. 1, 19–29 (2008).
Google Scholar
Singh, M. S. et al. Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation. Proc. Natl Acad. Sci. USA 110, 1101–1106 (2013).
Google Scholar
Garita-Hernandez, M. et al. Restoration of visual function by transplantation of optogenetically engineered photoreceptors. Nat. Commun. 10, 4524 (2019).
Google Scholar
Gust, J. & Reh, T. A. Adult donor rod photoreceptors integrate into the mature mouse retina. Invest. Ophthalmol. Vis. Sci. 52, 5266–5272 (2011).
Google Scholar
Singh, M. S. et al. Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion. Nat. Commun. 7, 13537 (2016).
Google Scholar
Santos-Ferreira, T. et al. Retinal transplantation of photoreceptors results in donor-host cytoplasmic exchange. Nat. Commun. 7, 13028 (2016).
Google Scholar
Pearson, R. A. et al. Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors. Nat. Commun. 7, 13029 (2016).
Google Scholar
Ortin-Martinez, A. et al. A reinterpretation of cell transplantation: GFP transfer from donor to host photoreceptors. Stem Cells 35, 932–939 (2017).
Google Scholar
Garweg, J. G., Tappeiner, C. & Halberstadt, M. Pathophysiology of proliferative vitreoretinopathy in retinal detachment. Surv. Ophthalmol. 58, 321–329 (2013).
Google Scholar
Li, L. & Turner, J. E. Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and long-term survival characteristics. Exp. Eye Res. 47, 771–785 (1988).
Google Scholar
Royo, P. E. & Quay, W. B. Retinal transplantation from fetal to maternal mammalian eye. Growth 23, 313–336 (1959).
Google Scholar
Kador, K. E. et al. Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold. Acta Biomater. 10, 4939–4946 (2014).
Google Scholar
Gandhi, J. K. et al. Fibrin hydrogels are safe, degradable scaffolds for sub-retinal implantation. PLoS ONE 15, e0227641 (2020).
Google Scholar
Ott, H. C. et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat. Med. 14, 213–221 (2008).
Google Scholar
Karczewski, M. & Malkiewicz, T. Scaffolds from surgically removed kidneys as a potential source of organ transplantation. Biomed. Res. Int. 2015, 325029 (2015).
Google Scholar
Kundu, J. et al. Decellularized retinal matrix: natural platforms for human retinal progenitor cell culture. Acta Biomater. 31, 61–70 (2016).
García Delgado, A. B. et al. Subretinal transplant of induced pluripotent stem cell-derived retinal pigment epithelium on nanostructured fibrin-agarose. Tissue Eng. Part A 25, 799–808 (2019).
Google Scholar
Krishna, Y. et al. Expanded polytetrafluoroethylene as a substrate for retinal pigment epithelial cell growth and transplantation in age-related macular degeneration. Br. J. Ophthalmol. 95, 569–573 (2011).
Google Scholar
Chedly, J. et al. Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. Biomaterials 138, 91–107 (2017).
Google Scholar
Caron, I. et al. A new three-dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury. Biomaterials 75, 135–147 (2016).
Google Scholar
Sakiyama-Elbert, S., Johnson, P. J., Hodgetts, S. I., Plant, G. W. & Harvey, A. R. Scaffolds to promote spinal cord regeneration. Handb. Clin. Neurol. 109, 575–594 (2012).
Google Scholar
Hong, L. T. A. et al. An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling. Nat. Commun. 8, 533 (2017).
Google Scholar
Masaeli, E. et al. Tissue engineering of retina through high resolution 3-dimensional inkjet bioprinting. Biofabrication 12, 025006 (2020).
Google Scholar
Singh, D. et al. A biodegradable scaffold enhances differentiation of embryonic stem cells into a thick sheet of retinal cells. Biomaterials 154, 158–168 (2018).
Google Scholar
Akiba, R. et al. Quantitative and qualitative evaluation of photoreceptor synapses in developing, degenerating and regenerating retinas. Front. Cell Neurosci. 13, 16 (2019).
Google Scholar
Omori, Y. et al. Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells. J. Neurosci. 32, 6126–6137 (2012).
Google Scholar
Nandrot, E. F., Chang, Y. & Finnemann, S. C. Alphavbeta5 integrin receptors at the apical surface of the RPE: one receptor, two functions. Adv. Exp. Med. Biol. 613, 369–375 (2008).
Google Scholar
Dorgau, B. et al. Decellularised extracellular matrix-derived peptides from neural retina and retinal pigment epithelium enhance the expression of synaptic markers and light responsiveness of human pluripotent stem cell derived retinal organoids. Biomaterials 199, 63–75 (2019).
Google Scholar
Jung, Y. H. et al. 3D microstructured scaffolds to support photoreceptor polarization and maturation. Adv. Mater. 30, e1803550 (2018).
Google Scholar
Bernardos, R. L., Barthel, L. K., Meyers, J. R. & Raymond, P. A. Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. J. Neurosci. 27, 7028–7040 (2007).
Google Scholar
Thummel, R., Kassen, S. C., Montgomery, J. E., Enright, J. M. & Hyde, D. R. Inhibition of Müller glial cell division blocks regeneration of the light-damaged zebrafish retina. Dev. Neurobiol. 68, 392–408 (2008).
Google Scholar
Johns, P. R. & Fernald, R. D. Genesis of rods in teleost fish retina. Nature 293, 141–142 (1981).
Google Scholar
Fischer, A. J. & Reh, T. A. Müller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat. Neurosci. 4, 247–252 (2001).
Google Scholar
Garber, K. RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat. Biotech. 33, 890–891 (2015).
Google Scholar
Spencer, R., Fisher, S., Lewis, G. P. & Malone, T. Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476). Clin. Ophthalmol. 11, 1797–1803 (2017).
Google Scholar
Oishi, A. et al. Retinal nerve fiber layer thickness in patients with retinitis pigmentosa. Eye 23, 561–566 (2009).
Google Scholar
Hood, D. C. et al. Thickness of receptor and post-receptor retinal layers in patients with retinitis pigmentosa measured with frequency-domain optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 50, 2328–2336 (2009).
Google Scholar
Punzo, C. & Cepko, C. Cellular responses to photoreceptor death in the rd1 mouse model of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 48, 849–857 (2007).
Google Scholar
MacLaren, R. E. Development and role of retinal glia in regeneration of ganglion cells following retinal injury. Br. J. Ophthalmol. 80, 458–464 (1996).
Google Scholar
Chua, J. et al. Early remodeling of Müller cells in the rd/rd mouse model of retinal dystrophy. J. Comp. Neurol. 521, 2439–2453 (2013).
Google Scholar
Kinouchi, R. et al. Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat. Neurosci. 6, 863–868 (2003).
Google Scholar
Lee, W. et al. The external limiting membrane in early-onset Stargardt disease. Invest. Ophthalmol. Vis. Sci. 55, 6139–6149 (2014).
Google Scholar
Pearson, R. A. et al. Targeted disruption of outer limiting membrane junctional proteins (Crb1 and ZO-1) increases integration of transplanted photoreceptor precursors into the adult wild-type and degenerating retina. Cell Transplant. 19, 487–503 (2010).
Google Scholar
Lao, L. L., Peppas, N. A., Boey, F. Y. & Venkatraman, S. S. Modeling of drug release from bulk-degrading polymers. Int. J. Pharm. 418, 28–41 (2011).
Google Scholar
Singh, R. K., Kolandaivelu, S. & Ramamurthy, V. Early alteration of retinal neurons in Aipl1−/− animals. Invest. Ophthalmol. Vis. Sci. 55, 3081–3092 (2014).
Google Scholar
Tansley, K. The development of the rat eye in graft. J. Exp. Biol. 22, 221–223 (1946).
Google Scholar
Humayun, M. S. et al. Human neural retinal transplantation. Invest. Ophthalmol. Vis. Sci. 41, 3100–3106 (2000).
Google Scholar
Tomita, M. et al. Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina. Stem Cells 20, 279–283 (2002).
Google Scholar
MacLaren, R. E. et al. Retinal repair by transplantation of photoreceptor precursors. Nature 444, 203–207 (2006).
Google Scholar
Lamba, D. A., Gust, J. & Reh, T. A. Transplantation of human embryonic stem cell derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell 4, 73–79 (2009).
Google Scholar
Lamba, D. A. et al. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS ONE 5, e8763 (2010).
Google Scholar
Eiraku, M. et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472, 51–56 (2011).
Google Scholar
Pearson, R. A. et al. Restoration of vision after transplantation of photoreceptors. Nature 485, 99–103 (2012).
Google Scholar
Howden, S. E. et al. Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy. Proc. Natl Acad. Sci. USA 108, 6537–6542 (2011).
Google Scholar
Barnea-Cramer, A. O. et al. Repair of retinal degeneration following ex vivo minicircle DNA gene therapy and transplantation of corrected photoreceptor progenitors. Mol. Ther. 28, 830–844 (2020).
Google Scholar
Naldini, L. Ex vivo gene transfer and correction for cell-based therapies. Nat. Rev. Genet. 12, 301–315 (2011).
Google Scholar
Chow, A. Y. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch. Ophthalmol. 122, 460–469 (2004).
Google Scholar
Guenther, T., Lovell, N. H. & Suaning, G. J. Bionic vision: system architectures: a review. Expert Rev. Med. Devices 9, 33–48 (2012).
Google Scholar
Garg, S. J. & Federman, J. Optogenetics, visual prosthesis and electrostimulation for retinal dystrophies. Curr. Opin. Ophthalmol. 24, 407–414 (2013).
Google Scholar
Luo, Y. H. & da Cruz, L. A review and update on the current status of retinal prostheses (bionic eye). Br. Med. Bull. 109, 31–44 (2014).
Google Scholar
Zrenner, E. Fighting blindness with microelectronics. Sci. Transl. Med. 5, 210ps16 (2013).
Google Scholar
Humayun, M. S. et al. Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vis. Res. 43, 2573–2581 (2003).
Google Scholar
Yanai, D. et al. Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am. J. Ophthalmol. 143, 820–827 (2007).
Google Scholar
Rizzo, J. F. III, Wyatt, J., Loewenstein, J., Kelly, S. & Shire, D. Perceptual efficacy of electrical stimulation of human retina with a microelectrode array during short-term surgical trials. Invest. Ophthalmol. Vis. Sci. 44, 5362–5369 (2003).
Google Scholar
Humayun, M. S. et al. Preliminary 6 month results from the Argus II epiretinal prosthesis feasibility study. Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. 4566–4568 (2009).
Ho, A. C. et al. Argus II Study Group. LONG-term results from an epiretinal prosthesis to restore sight to the blind. Ophthalmology 122, 1547–1554 (2015).
Google Scholar
Humayun, M. S. et al. Argus II Study Group. Interim results from the international trial of Second Sight’s visual prosthesis. Ophthalmology 119, 779–788 (2012).
Richard, G. et al. Multicenter study on acute electrical stimulation of the human retina with an epiretinal implant: clinical results in 20 patients. Invest. Ophthalmol. Vis. Sci. 46, 1143 (2005).
Keserü, M. et al. Acute electrical stimulation of the human retina with an epiretinal electrode array. Acta Ophthalmol. 90, e1–e8 (2012).
Google Scholar
da Cruz, L. et al. Five-year safety and performance results from the Argus II retinal prosthesis system clinical trial. Argus II Study Group. Ophthalmology 123, 2248–2254 (2016).
Google Scholar
Zrenner, E. et al. Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc. Biol. Sci. 278, 1489–1497 (2011).
Google Scholar
Roessler, G. et al. Implantation and explantation of a wireless epiretinal retina implant device in blind RP patients. Invest. Ophthalmol. Vis. Sci. 50, 3003–3008 (2009).
Google Scholar
Stingl, K. et al. Subretinal visual implant Alpha IMS–clinical trial interim report. Vis. Res. 111, 149–160 (2015).
Google Scholar
Stingl, K. et al. Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc. Biol. Sci. 280, 20130077 (2013).
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
Edwards, T. L. et al. Assessment of the electronic retinal implant Alpha AMS in restoring vision to blind patients with end-stage retinitis pigmentosa. Ophthalmology 125, 432–443 (2018).
Google Scholar
Ayton, L. N. et al. Bionic Vision Australia Research Consortium. First-in-human trial of a novel suprachoroidal retinal prosthesis. PLoS ONE 9, e115239 (2014).
Google Scholar
Fujikado, T. et al. Testing of semichronically implanted retinal prosthesis by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 52, 4726–4733 (2011).
Google Scholar
Abbott, C. J. et al. Safety studies for a 44-channel suprachoroidal retinal prosthesis: a chronic passive study. Invest. Ophthalmol. Vis. Sci. 59, 1410–1424 (2018).
Google Scholar
MacLaren, R. E. Electronic retinal implant surgery. Eye 31, 191–195 (2017).
Google Scholar
Mathieson, K. et al. Photovoltaic retinal prosthesis with high pixel density. Nat. Photonics 6, 391–397 (2012).
Google Scholar
Perez Fornos, A., Sommerhalder, J., Pittard, A., Safran, A. B. & Pelizzone, M. Simulation of artificial vision: IV. Visual information required to achieve simple pointing and manipulation tasks. Vis. Res. 48, 1705–1718 (2008).
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).
Duncan, J. L. et al. Improvements in vision-related quality of life in blind patients implanted with the Argus II epiretinal prosthesis. Clin. Exp. Optom. 100, 144–150 (2017).
Google Scholar
Dagnelie, G. et al. Argus® II Study Group. Performance of real-world functional vision tasks by blind subjects improves after implantation with the Argus® II retinal prosthesis system. Clin. Exp. Ophthalmol. 45, 152–159 (2017).
Google Scholar
da Cruz, L. et al. Argus II Study Group. Five-year safety and performance results from the Argus II retinal prosthesis system clinical trial. Ophthalmology 123, 2248–2254 (2016).
Google Scholar
Luo, Y. H., Zhong, J. J. & da Cruz, L. The use of Argus® II retinal prosthesis by blind subjects to achieve localisation and prehension of objects in 3-dimensional space. Graefes Arch. Clin. Exp. Ophthalmol. 253, 1907–1914 (2015).
Google Scholar
Kotecha, A., Zhong, J., Stewart, D. & da Cruz, L. The Argus II prosthesis facilitates reaching and grasping tasks: a case series. BMC Ophthalmol. 14, 71 (2014).
Google Scholar
da Cruz, L. et al. Argus II Study Group. The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss. Br. J. Ophthalmol. 97, 632–636 (2013).
Google Scholar
Dorn, J. D. et al. Argus II Study Group. The detection of motion by blind subjects with the epiretinal 60-electrode (Argus II) retinal prosthesis. JAMA Ophthalmol. 131, 183–189 (2013).
Google Scholar
Geruschat, D. R. et al. An analysis of observer-rated functional vision in patients implanted with the Argus II retinal prosthesis system at three years. Clin. Exp. Optom. 99, 227–232 (2016).
Google Scholar
Jensen, R. J., Rizzo, J. F. III, Ziv, O. R., Grumet, A. & Wyatt, J. Thresholds for activation of rabbit retinal ganglion cells with an ultrafine, extracellular microelectrode. Invest. Ophthalmol. Vis. Sci. 44, 3533–3543 (2003).
Google Scholar
Brindley, G. S. & Lewin, W. S. The visual sensations produced by electrical stimulation of the medial occipital cortex. J. Physiol. 194, 54-5P (1968).
Dobelle, W. H., Mladejovsky, M. G. & Girvin, J. P. Artifical vision for the blind: electrical stimulation of visual cortex offers hope for a functional prosthesis. Science 183, 440–444 (1974).
Google Scholar
Lewis, P. M. & Rosenfeld, J. V. Electrical stimulation of the brain and the development of cortical visual prostheses: an historical perspective. Brain Res. 1630, 208–224 (2016).
Google Scholar
Bradley, D. C. et al. Visuotopic mapping through a multichannel stimulating implant in primate V1. J. Neurophys. 93, 1659–1670 (2005).
Google Scholar
Niketeghad, S. & Pouratian, N. Brain machine interfaces for vision restoration: the current state of cortical visual prosthetics. Neurotherapeutics 16, 134–143 (2019).
Google Scholar
Rosenfeld, J. V. et al. Tissue response to a chronically implantable wireless intracortical visual prosthesis (Gennaris array). J. Neural Eng. 17, 046001 (2020).
Google Scholar
Fernández, E & Normann, R. in Artificial Vision (ed. Gabel, V. P.) 191–201 (Springer, 2017).
Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019).
Google Scholar
Zhu, J. et al. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors. Cell Res. 27, 830–833 (2017).
Google Scholar
Edwards, T. L. et al. First-in-human study of the safety and viability of intraocular robotic surgery. Nat. Biomed. Eng. 2, 649–656 (2018).
Google Scholar
Cehajic-Kapetanovic, J. et al. First-in-human robot-assisted subretinal drug delivery under local anaesthesia: a randomisedclinical trial. Am. J. Ophthalmol. https://doi.org/10.1016/j.ajo.2021.11.011 (2021).
Mayoral, S. R., Etxeberria, A., Shen, Y. A. & Chan, J. R. Initiation of CNS myelination in the optic nerve is dependent on axon caliber. Cell Rep. 25, 544–550.e3 (2018).
Google Scholar
Ayton, L. N. et al. Harmonization of outcomes and vision endpoints in vision restoration trials: recommendations from the International HOVER Taskforce. Transl. Vis. Sci. Technol. 9, 25 (2020).
Google Scholar
Maya-Vetencourt, J. F. et al. A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness. Nat. Mater. 16, 681–689 (2017).
Google Scholar
Ha, S. et al. Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry. J. Neural Eng. 13, 056008 (2016).
Google Scholar
Samba, R., Herrmann, T. & Zeck, G. PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities. J. Neural Eng. 12, 016014 (2015).
Google Scholar
Jones, P. D. & Stelzle, M. Can nanofluidic chemical release enable fast, high resolution neurotransmitter-based neurostimulation? Front. Neurosci. 10, 138 (2016).
Google Scholar
Albert, E. S. et al. TRPV4 channels mediate the infrared laser-evoked response in sensory neurons. J. Neurophysiol. 107, 3227–3234 (2012).
Google Scholar
Bonmassar, G. et al. Microscopic magnetic stimulation of neural tissue. Nat. Commun. 3, 921 (2012).
Google Scholar
Holladay, J. T. Visual acuity measurements. J. Cataract Refract. Surg. 30, 287–290 (2004).
Google Scholar

