Preloader

Bioengineering strategies for restoring vision

  • 1.

    Sohocki, M. M. et al. Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum. Mutat. 17, 42–51 (2001).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 2.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 3.

    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).

    PubMed 

    Google Scholar 

  • 4.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 5.

    Xue, K. et al. Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia. Nat. Med. 24, 1507–1512 (2018).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 6.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 7.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 8.

    Kantor, A. et al. CRISPR genome engineering for retinal diseases. Prog. Mol. Biol. Transl. Sci. 182, 29–79 (2021).

    PubMed 
    CAS 

    Google Scholar 

  • 9.

    Quinn, J. et al. Genome-editing strategies for treating human retinal degenerations. Hum. Gene Ther. 32, 247–259 (2021).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 10.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 11.

    Jonas, J. B. et al. Glaucoma. Lancet 390, 2183–2193 (2017).

    PubMed 

    Google Scholar 

  • 12.

    Guy, J. et al. Gene therapy for Leber hereditary optic neuropathy: low- and medium-dose visual results. Ophthalmology 124, 1621–1634 (2017).

    PubMed 

    Google Scholar 

  • 13.

    Vignal, C. et al. Safety of rAAV2/2-ND4 gene therapy for Leber hereditary optic neuropathy. Ophthalmology 125, 945–947 (2018).

    PubMed 

    Google Scholar 

  • 14.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 15.

    Zhang, X. et al. Cell transplantation of retinal ganglion cells derived from hESCs. Restor. Neurol. Neurosci. 38, 131–140 (2020).

    PubMed 

    Google Scholar 

  • 16.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 17.

    Jones, B. W. et al. Retinal remodeling triggered by photoreceptor degenerations. J. Comp. Neurol. 464, 1–16 (2003).

    PubMed 

    Google Scholar 

  • 18.

    Marc, R. E. & Jones, B. W. Retinal remodeling in inherited photoreceptor degenerations. Mol. Neurobiol. 28, 139–147 (2003).

    PubMed 
    CAS 

    Google Scholar 

  • 19.

    Marc, R. E., Jones, B. W., Watt, C. B. & Strettoi, E. Neural remodeling in retinal degeneration. Prog. Retin. Eye Res. 22, 607–655 (2003).

    PubMed 

    Google Scholar 

  • 20.

    Jones, B. W. & Marc, R. E. Retinal remodeling during retinal degeneration. Exp. Eye Res. 81, 123–137 (2005).

    PubMed 
    CAS 

    Google Scholar 

  • 21.

    Marc, R. E. et al. Neural reprogramming in retinal degeneration. Invest. Ophthalmol. Vis. Sci. 48, 3364–3371 (2007).

    PubMed 

    Google Scholar 

  • 22.

    Cuenca, N. et al. Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases. Prog. Retin. Eye Res. 43, 17–75 (2014).

    PubMed 
    CAS 

    Google Scholar 

  • 23.

    Jones, B. W. et al. Retinal remodeling in human retinitis pigmentosa. Exp. Eye Res. 150, 149–165 (2016).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 24.

    Krishnamoorthy, V. et al. Retinal remodeling: concerns, emerging remedies and future prospects. Front. Cell Neurosci. 10, 38 (2016).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 25.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 26.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 27.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 28.

    Acland, G. M. et al. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28, 92–95 (2001).

    PubMed 
    CAS 

    Google Scholar 

  • 29.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 30.

    Maguire, A. M. et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N. Engl. J. Med. 358, 2240–2248 (2008).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 31.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 32.

    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).

    PubMed 

    Google Scholar 

  • 33.

    Josan, A. S. et al. Microperimetry Hill of vision and volumetric measures of retinal sensitivity. Transl. Vis. Sci. Technol. 10, 12 (2021).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 34.

    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).

    Google Scholar 

  • 35.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 36.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 37.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 38.

    T Trapani, I. et al. Effective delivery of large genes to the retina by dual AAV vectors. EMBO Mol. Med. 6, 194–211 (2014).

    Google Scholar 

  • 39.

    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).

    Google Scholar 

  • 40.

    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).

    PubMed Central 
    CAS 

    Google Scholar 

  • 41.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 42.

    Sander, J. D. & Joung, J. K. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol. 32, 347–355 (2014).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 43.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 44.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 45.

    Tsai, Y. et al. CRISPR-based genome surgery for the treatment of autosomal dominant retinitis. Ophthalmology 125, 1421–1430 (2018).

    PubMed 

    Google Scholar 

  • 46.

    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).

    Google Scholar 

  • 47.

    Bi, A. et al. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50, 23–33 (2006).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 48.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 49.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 50.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 51.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 52.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 53.

    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).

    PubMed 

    Google Scholar 

  • 54.

    Busskamp, V. et al. Genetic rectivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329, 413–417 (2010).

    PubMed 
    CAS 

    Google Scholar 

  • 55.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 56.

    Sahel, J. A. et al. Partial recovery of visual function in a blind patient after optogenetic therapy. Nat. Med. 27, 1223–1229 (2021).

    PubMed 
    CAS 

    Google Scholar 

  • 57.

    Cehajic-Kapetanovic, J. et al. Restoration of vision with ectopic expression of human rod opsin. Curr. Biol. 25, 2111–2122 (2015).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 58.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 59.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 60.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 61.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 62.

    Berry, M. H. et al. Restoration of high-sensitivity and adapting vision with a cone opsin. Nat. Commun. 10, 1221 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 63.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 64.

    Berry, M. H. et al. Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor. Nat. Commun. 8, 1862 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 65.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 66.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 67.

    Cehajic-Kapetanovic, J. et al. Glycosidic enzymes enhance retinal transduction following intravitreal delivery of AAV2. Mol. Vis. 17, 1771–1783 (2011).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 68.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 69.

    Fick, A. ‘On liquid diffusion’. Ann. Phys. Chem. 94, 59 (1855).

    Google Scholar 

  • 70.

    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).

    PubMed 

    Google Scholar 

  • 71.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 72.

    Cehajic-Kapetanovic, J. et al. Highest reported visual acuity after electronic retinal implantation. Acta Ophthalmol. 98, 736–740 (2020).

    PubMed 

    Google Scholar 

  • 73.

    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).

  • 74.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 75.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 76.

    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).

    PubMed 

    Google Scholar 

  • 77.

    Park, S. S. Cell therapy applications for retinal vascular diseases: diabetic retinopathy and retinal vein occlusion. Invest. Ophthalmol. Vis. Sci. 57, ORSFj1–ORSFj10 (2016).

    PubMed 
    CAS 

    Google Scholar 

  • 78.

    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).

    PubMed 

    Google Scholar 

  • 79.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 80.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 81.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 82.

    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).

    PubMed Central 

    Google Scholar 

  • 83.

    Zhou, J. et al. Retinal progenitor cells release extracellular vesicles containing developmental transcription factors, microRNA and membrane proteins. Sci. Rep. 8, 2823 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 84.

    Knickelbein, J. E. et al. Modulation of immune responses by extracellular vesicles from retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 57, 4101–4107 (2016).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 85.

    Kashani, A. H. et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration. Sci. Transl. Med. 10, eaao4097 (2018).

    PubMed 

    Google Scholar 

  • 86.

    Mandai, M. et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 376, 1038–1046 (2017).

    PubMed 
    CAS 

    Google Scholar 

  • 87.

    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).

    PubMed 

    Google Scholar 

  • 88.

    Schwartz, S. D. et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379, 713–720 (2012).

    PubMed 
    CAS 

    Google Scholar 

  • 89.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 90.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 91.

    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).

    Google Scholar 

  • 92.

    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).

    Google Scholar 

  • 93.

    Yang, J. et al. Translational development of human retinal progenitor cells for treatment of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 54, 2237 (2013).

    Google Scholar 

  • 94.

    Warfvinge, K. et al. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs. J. Transplant. 2011, 948740 (2011).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 95.

    Aftab, U. et al. Growth kinetics and transplantation of human retinal progenitor cells. Exp. Eye Res. 89, 301–310 (2009).

    PubMed 
    CAS 

    Google Scholar 

  • 96.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 97.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 98.

    Garita-Hernandez, M. et al. Restoration of visual function by transplantation of optogenetically engineered photoreceptors. Nat. Commun. 10, 4524 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 99.

    Gust, J. & Reh, T. A. Adult donor rod photoreceptors integrate into the mature mouse retina. Invest. Ophthalmol. Vis. Sci. 52, 5266–5272 (2011).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 100.

    Singh, M. S. et al. Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion. Nat. Commun. 7, 13537 (2016).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 101.

    Santos-Ferreira, T. et al. Retinal transplantation of photoreceptors results in donor-host cytoplasmic exchange. Nat. Commun. 7, 13028 (2016).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 102.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 103.

    Ortin-Martinez, A. et al. A reinterpretation of cell transplantation: GFP transfer from donor to host photoreceptors. Stem Cells 35, 932–939 (2017).

    PubMed 
    CAS 

    Google Scholar 

  • 104.

    Garweg, J. G., Tappeiner, C. & Halberstadt, M. Pathophysiology of proliferative vitreoretinopathy in retinal detachment. Surv. Ophthalmol. 58, 321–329 (2013).

    PubMed 

    Google Scholar 

  • 105.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 106.

    Royo, P. E. & Quay, W. B. Retinal transplantation from fetal to maternal mammalian eye. Growth 23, 313–336 (1959).

    PubMed 
    CAS 

    Google Scholar 

  • 107.

    Kador, K. E. et al. Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold. Acta Biomater. 10, 4939–4946 (2014).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 108.

    Gandhi, J. K. et al. Fibrin hydrogels are safe, degradable scaffolds for sub-retinal implantation. PLoS ONE 15, e0227641 (2020).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 109.

    Ott, H. C. et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat. Med. 14, 213–221 (2008).

    PubMed 
    CAS 

    Google Scholar 

  • 110.

    Karczewski, M. & Malkiewicz, T. Scaffolds from surgically removed kidneys as a potential source of organ transplantation. Biomed. Res. Int. 2015, 325029 (2015).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 111.

    Kundu, J. et al. Decellularized retinal matrix: natural platforms for human retinal progenitor cell culture. Acta Biomater. 31, 61–70 (2016).

  • 112.

    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).

    PubMed 

    Google Scholar 

  • 113.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 114.

    Chedly, J. et al. Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. Biomaterials 138, 91–107 (2017).

    PubMed 
    CAS 

    Google Scholar 

  • 115.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 116.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 117.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 118.

    Masaeli, E. et al. Tissue engineering of retina through high resolution 3-dimensional inkjet bioprinting. Biofabrication 12, 025006 (2020).

    PubMed 
    CAS 

    Google Scholar 

  • 119.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 120.

    Akiba, R. et al. Quantitative and qualitative evaluation of photoreceptor synapses in developing, degenerating and regenerating retinas. Front. Cell Neurosci. 13, 16 (2019).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 121.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 122.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 123.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 124.

    Jung, Y. H. et al. 3D microstructured scaffolds to support photoreceptor polarization and maturation. Adv. Mater. 30, e1803550 (2018).

    PubMed 

    Google Scholar 

  • 125.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 126.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 127.

    Johns, P. R. & Fernald, R. D. Genesis of rods in teleost fish retina. Nature 293, 141–142 (1981).

    PubMed 
    CAS 

    Google Scholar 

  • 128.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 129.

    Garber, K. RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat. Biotech. 33, 890–891 (2015).

    CAS 

    Google Scholar 

  • 130.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 131.

    Oishi, A. et al. Retinal nerve fiber layer thickness in patients with retinitis pigmentosa. Eye 23, 561–566 (2009).

    PubMed 
    CAS 

    Google Scholar 

  • 132.

    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).

    PubMed 

    Google Scholar 

  • 133.

    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).

    PubMed 

    Google Scholar 

  • 134.

    MacLaren, R. E. Development and role of retinal glia in regeneration of ganglion cells following retinal injury. Br. J. Ophthalmol. 80, 458–464 (1996).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 135.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 136.

    Kinouchi, R. et al. Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat. Neurosci. 6, 863–868 (2003).

    PubMed 
    CAS 

    Google Scholar 

  • 137.

    Lee, W. et al. The external limiting membrane in early-onset Stargardt disease. Invest. Ophthalmol. Vis. Sci. 55, 6139–6149 (2014).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 138.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 139.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 140.

    Singh, R. K., Kolandaivelu, S. & Ramamurthy, V. Early alteration of retinal neurons in Aipl1−/− animals. Invest. Ophthalmol. Vis. Sci. 55, 3081–3092 (2014).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 141.

    Tansley, K. The development of the rat eye in graft. J. Exp. Biol. 22, 221–223 (1946).

    PubMed 
    CAS 

    Google Scholar 

  • 142.

    Humayun, M. S. et al. Human neural retinal transplantation. Invest. Ophthalmol. Vis. Sci. 41, 3100–3106 (2000).

    PubMed 
    CAS 

    Google Scholar 

  • 143.

    Tomita, M. et al. Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina. Stem Cells 20, 279–283 (2002).

    PubMed 
    CAS 

    Google Scholar 

  • 144.

    MacLaren, R. E. et al. Retinal repair by transplantation of photoreceptor precursors. Nature 444, 203–207 (2006).

    PubMed 
    CAS 

    Google Scholar 

  • 145.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 146.

    Lamba, D. A. et al. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS ONE 5, e8763 (2010).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 147.

    Eiraku, M. et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472, 51–56 (2011).

    PubMed 
    CAS 

    Google Scholar 

  • 148.

    Pearson, R. A. et al. Restoration of vision after transplantation of photoreceptors. Nature 485, 99–103 (2012).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 149.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 150.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 151.

    Naldini, L. Ex vivo gene transfer and correction for cell-based therapies. Nat. Rev. Genet. 12, 301–315 (2011).

    PubMed 
    CAS 

    Google Scholar 

  • 152.

    Chow, A. Y. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch. Ophthalmol. 122, 460–469 (2004).

    PubMed 

    Google Scholar 

  • 153.

    Guenther, T., Lovell, N. H. & Suaning, G. J. Bionic vision: system architectures: a review. Expert Rev. Med. Devices 9, 33–48 (2012).

    PubMed 

    Google Scholar 

  • 154.

    Garg, S. J. & Federman, J. Optogenetics, visual prosthesis and electrostimulation for retinal dystrophies. Curr. Opin. Ophthalmol. 24, 407–414 (2013).

    PubMed 

    Google Scholar 

  • 155.

    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).

    PubMed 

    Google Scholar 

  • 156.

    Zrenner, E. Fighting blindness with microelectronics. Sci. Transl. Med. 5, 210ps16 (2013).

    PubMed 

    Google Scholar 

  • 157.

    Humayun, M. S. et al. Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vis. Res. 43, 2573–2581 (2003).

    PubMed 

    Google Scholar 

  • 158.

    Yanai, D. et al. Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am. J. Ophthalmol. 143, 820–827 (2007).

    PubMed 

    Google Scholar 

  • 159.

    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).

    PubMed 

    Google Scholar 

  • 160.

    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).

  • 161.

    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).

    PubMed 

    Google Scholar 

  • 162.

    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).

  • 163.

    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).

    Google Scholar 

  • 164.

    Keserü, M. et al. Acute electrical stimulation of the human retina with an epiretinal electrode array. Acta Ophthalmol. 90, e1–e8 (2012).

    PubMed 

    Google Scholar 

  • 165.

    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).

    PubMed 

    Google Scholar 

  • 166.

    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).

    PubMed 

    Google Scholar 

  • 167.

    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).

    PubMed 

    Google Scholar 

  • 168.

    Stingl, K. et al. Subretinal visual implant Alpha IMS–clinical trial interim report. Vis. Res. 111, 149–160 (2015).

    PubMed 

    Google Scholar 

  • 169.

    Stingl, K. et al. Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc. Biol. Sci. 280, 20130077 (2013).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 170.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 171.

    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).

    PubMed 

    Google Scholar 

  • 172.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 173.

    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).

    PubMed 

    Google Scholar 

  • 174.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 175.

    MacLaren, R. E. Electronic retinal implant surgery. Eye 31, 191–195 (2017).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 176.

    Mathieson, K. et al. Photovoltaic retinal prosthesis with high pixel density. Nat. Photonics 6, 391–397 (2012).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 177.

    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).

    PubMed 

    Google Scholar 

  • 178.

    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).

  • 179.

    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).

    PubMed 

    Google Scholar 

  • 180.

    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).

    PubMed 

    Google Scholar 

  • 181.

    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).

    PubMed 

    Google Scholar 

  • 182.

    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).

    PubMed 

    Google Scholar 

  • 183.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 184.

    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).

    PubMed 

    Google Scholar 

  • 185.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 186.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 187.

    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).

    PubMed 

    Google Scholar 

  • 188.

    Brindley, G. S. & Lewin, W. S. The visual sensations produced by electrical stimulation of the medial occipital cortex. J. Physiol. 194, 54-5P (1968).

  • 189.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 190.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 191.

    Bradley, D. C. et al. Visuotopic mapping through a multichannel stimulating implant in primate V1. J. Neurophys. 93, 1659–1670 (2005).

    CAS 

    Google Scholar 

  • 192.

    Niketeghad, S. & Pouratian, N. Brain machine interfaces for vision restoration: the current state of cortical visual prosthetics. Neurotherapeutics 16, 134–143 (2019).

    PubMed 
    CAS 

    Google Scholar 

  • 193.

    Rosenfeld, J. V. et al. Tissue response to a chronically implantable wireless intracortical visual prosthesis (Gennaris array). J. Neural Eng. 17, 046001 (2020).

    PubMed 

    Google Scholar 

  • 194.

    Fernández, E & Normann, R. in Artificial Vision (ed. Gabel, V. P.) 191–201 (Springer, 2017).

  • 195.

    Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 196.

    Zhu, J. et al. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors. Cell Res. 27, 830–833 (2017).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 197.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 198.

    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).

  • 199.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 200.

    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).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 201.

    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).

    PubMed 
    PubMed Central 
    CAS 

    Google Scholar 

  • 202.

    Ha, S. et al. Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry. J. Neural Eng. 13, 056008 (2016).

    PubMed 

    Google Scholar 

  • 203.

    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).

    PubMed 
    CAS 

    Google Scholar 

  • 204.

    Jones, P. D. & Stelzle, M. Can nanofluidic chemical release enable fast, high resolution neurotransmitter-based neurostimulation? Front. Neurosci. 10, 138 (2016).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 205.

    Albert, E. S. et al. TRPV4 channels mediate the infrared laser-evoked response in sensory neurons. J. Neurophysiol. 107, 3227–3234 (2012).

    PubMed 
    CAS 

    Google Scholar 

  • 206.

    Bonmassar, G. et al. Microscopic magnetic stimulation of neural tissue. Nat. Commun. 3, 921 (2012).

    PubMed 

    Google Scholar 

  • 207.

    Holladay, J. T. Visual acuity measurements. J. Cataract Refract. Surg. 30, 287–290 (2004).

    PubMed 

    Google Scholar 

  • Source link