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Restoring vision

Nature volume 557, pages 359–367 (2018)Cite this article

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Abstract

Restoring vision to the blind by retinal repair has been a dream of medicine for centuries, and the first successful procedures have recently been performed. Although we are still far from the restoration of high-resolution vision, step-by-step developments are overcoming crucial bottlenecks in therapy development and have enabled the restoration of some visual function in patients with specific blindness-causing diseases. Here, we discuss the current state of vision restoration and the problems related to retinal repair. We describe new model systems and translational technologies, as well as the clinical conditions in which new methods may help to combat blindness.

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Fig. 1: The human retina in vivo.
Fig. 2: Cell types, circuits and computations performed by the vertebrate retina.
Fig. 3: Current and planned tools for treating blinding diseases.

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References

  1. The Lasker Foundation. Restoring Vision to the Blind http://www.laskerfoundation.org/new-noteworthy/articles/restoring-vision-blind/ (2015).

  2. Olson, R. J. Cataract surgery from 1918 to the present and future—just imagine! Am. J. Ophthalmol. 185, 10–13 (2017).

    PubMed  Google Scholar 

  3. Jager, R. D., Mieler, W. F. & Miller, J. W. Age-related macular degeneration. N. Engl. J. Med. 358, 2606–2617 (2008).

    CAS  PubMed  Google Scholar 

  4. Hodgson, N. et al. Economic and quality of life benefits of anti-VEGF therapy. Mol. Pharm. 13, 2877–2880 (2016).

    CAS  PubMed  Google Scholar 

  5. Finger, R. P., Guymer, R. H., Gillies, M. C. & Keeffe, J. E. The impact of anti-vascular endothelial growth factor treatment on quality of life in neovascular age-related macular degeneration. Ophthalmology 121, 1246–1251 (2014).

    PubMed  Google Scholar 

  6. Essue, B. M. et al. A multicenter prospective cohort study of quality of life and economic outcomes after cataract surgery in Vietnam: the VISIONARY study. Ophthalmology 121, 2138–2146 (2014).

    PubMed  Google Scholar 

  7. Lamoureux, E. L., Fenwick, E., Pesudovs, K. & Tan, D. The impact of cataract surgery on quality of life. Curr. Opin. Ophthalmol. 22, 19–27 (2011).

    PubMed  Google Scholar 

  8. WHO. Visual Impairment and Blindness http://www.who.int/mediacentre/factsheets/fs282/en/ (2017).

  9. 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).

    CAS  PubMed  Google Scholar 

  10. Hauswirth, W. W. et al. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum. Gene Ther. 19, 979–990 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Maguire, A. M. et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N. Engl. J. Med. 358, 2240–2248 (2008).This study led to the first FDA-approved AAV gene therapy.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 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).The first FDA-approved AAV gene therapy.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ashtari, M. et al. The human visual cortex responds to gene therapy-mediated recovery of retinal function. J. Clin. Invest. 121, 2160–2168 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Ashtari, M. et al. Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis. Sci. Transl. Med. 7, 296ra110 (2015).

    PubMed  PubMed Central  Google Scholar 

  15. Ledford, H. FDA advisers back gene therapy for rare form of blindness. Nature 550, 314 (2017).

    ADS  CAS  PubMed  Google Scholar 

  16. MacLaren, R. E. et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet 383, 1129–1137 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Edwards, T. L. et al. Visual acuity after retinal gene therapy for choroideremia. N. Engl. J. Med. 374, 1996–1998 (2016).

    PubMed  PubMed Central  Google Scholar 

  18. Humayun, M. S. et al. Visual perception elicited by electrical stimulation of retina in blind humans. Arch. Ophthalmol. 114, 40–46 (1996).This work led to the development of epiretinal implants.

    CAS  PubMed  Google Scholar 

  19. Mills, J. O., Jalil, A. & Stanga, P. E. Electronic retinal implants and artificial vision: journey and present. Eye 31, 1383–1398 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. da Cruz, L. et al. Five-year safety and performance results from the Argus II retinal prosthesis system clinical trial. Ophthalmology 123, 2248–2254 (2016).

    PubMed  Google Scholar 

  21. 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).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  23. Tanna, P., Strauss, R. W., Fujinami, K. & Michaelides, M. Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. Br. J. Ophthalmol. 101, 25–30 (2017).

    PubMed  Google Scholar 

  24. Daley, G. Q. Polar extremes in the clinical use of stem cells. N. Engl. J. Med. 376, 1075–1077 (2017).

    PubMed  Google Scholar 

  25. Espinosa, J. S. & Stryker, M. P. Development and plasticity of the primary visual cortex. Neuron 75, 230–249 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ganesh, S. et al. Results of late surgical intervention in children with early-onset bilateral cataracts. Br. J. Ophthalmol. 98, 1424–1428 (2014).

    PubMed  Google Scholar 

  27. Kalia, A. et al. Development of pattern vision following early and extended blindness. Proc. Natl Acad. Sci. USA 111, 2035–2039 (2014).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sinha, P., Chatterjee, G., Gandhi, T. & Kalia, A. Restoring vision through “Project Prakash”: the opportunities for merging science and service. PLoS Biol. 11, e1001741 (2013).

    PubMed  PubMed Central  Google Scholar 

  29. Wan, J. & Goldman, D. Retina regeneration in zebrafish. Curr. Opin. Genet. Dev. 40, 41–47 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Azeredo da Silveira, R. & Roska, B. Cell types, circuits, computation. Curr. Opin. Neurobiol. 21, 664–671 (2011).

    CAS  PubMed  Google Scholar 

  31. Masland, R. H. The neuronal organization of the retina. Neuron 76, 266–280 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Zeng, H. & Sanes, J. R. Neuronal cell-type classification: challenges, opportunities and the path forward. Nat. Rev. Neurosci. 18, 530–546 (2017).

    CAS  PubMed  Google Scholar 

  33. Seung, H. S. & Sümbül, U. Neuronal cell types and connectivity: lessons from the retina. Neuron 83, 1262–1272 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Weinmann, J. & Grimm, D. Next-generation AAV vectors for clinical use: an ever-accelerating race. Virus Genes 53, 707–713 (2017).

    CAS  PubMed  Google Scholar 

  35. Santos-Ferreira, T. F., Borsch, O. & Ader, M. Rebuilding the missing part—a review on photoreceptor transplantation. Front. Syst. Neurosci. 10, 105 (2017).

    PubMed  PubMed Central  Google Scholar 

  36. Chalupa, L. M. & Williams, R. W. (eds) Eye, Retina, and Visual System of the Mouse (MIT Press, Cambridge, 2008).

  37. Dacey, D. M. The mosaic of midget ganglion cells in the human retina. J. Neurosci. 13, 5334–5355 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Kolb, H. in Webvision: The Organization of the Retina and Visual System (eds Kolb, H. et al.) (Univ. Utah Health Sciences Center, Salt Lake City, 1995).

  39. Sahly, I. et al. Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice. J. Cell Biol. 199, 381–399 (2012).Example of the limitations of mice as a disease model.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Siegert, S. et al. Transcriptional code and disease map for adult retinal cell types. Nat. Neurosci. 15, 487–495 (2012).

    CAS  PubMed  Google Scholar 

  41. Kostic, C. & Arsenijevic, Y. Animal modelling for inherited central vision loss. J. Pathol. 238, 300–310 (2016).

    PubMed  Google Scholar 

  42. Kolb, H., Fernandez, E. & Nelson, R. (eds) Webvision: The Organization of the Retina and Visual System (Univ. Utah Health Sciences Center, Salt Lake City, 1995).

  43. Seiple, W., Rosen, R. B. & Garcia, P. M. T. Abnormal fixation in individuals with age-related macular degeneration when viewing an image of a face. Optom. Vis. Sci. 90, 45–56 (2013).

    PubMed  Google Scholar 

  44. Dalkara, D. et al. Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous. Mol. Ther. 17, 2096–2102 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 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 

  46. Yin, L. et al. Intravitreal injection of AAV2 transduces macaque inner retina. Invest. Ophthalmol. Vis. Sci. 52, 2775–2783 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Panda-Jonas, S., Jonas, J. B., Jakobczyk, M. & Schneider, U. Retinal photoreceptor count, retinal surface area, and optic disc size in normal human eyes. Ophthalmology 101, 519–523 (1994).

    CAS  PubMed  Google Scholar 

  48. Remtulla, S. & Hallett, P. E. A schematic eye for the mouse, and comparisons with the rat. Vision Res. 25, 21–31 (1985).

    CAS  PubMed  Google Scholar 

  49. Eiraku, M. et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472, 51–56 (2011).This study led to the development of human retinal organoids.

    ADS  CAS  PubMed  Google Scholar 

  50. Nakano, T. et al. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10, 771–785 (2012).

    CAS  PubMed  Google Scholar 

  51. Sasai, Y. Grow your own eye: biologists have coaxed cells to form a retina, a step toward growing replacement organs outside the body. Sci. Am. 307, 44–49 (2012).

    PubMed  Google Scholar 

  52. Ovando-Roche, P., Georgiadis, A., Smith, A. J., Pearson, R. A. & Ali, R. R. Harnessing the potential of human pluripotent stem cells and gene editing for the treatment of retinal degeneration. Curr. Stem Cell Rep. 3, 112–123 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Kaewkhaw, R. et al. Transcriptome dynamics of developing photoreceptors in three-dimensional retina cultures recapitulates temporal sequence of human cone and rod differentiation revealing cell surface markers and gene networks. Stem Cells 33, 3504–3518 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Busskamp, V. et al. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329, 413–417 (2010).Demonstration of optogenetic vision restoration in human retinas.

    ADS  CAS  PubMed  Google Scholar 

  55. Fradot, M. et al. Gene therapy in ophthalmology: validation on cultured retinal cells and explants from postmortem human eyes. Hum. Gene Ther. 22, 587–593 (2011).

    CAS  PubMed  Google Scholar 

  56. Dowling, J. E. The Retina (Harvard Univ. Press, Cambridge, 2012)

  57. Izpisua Belmonte, J. C. et al. Brains, genes, and primates. Neuron 86, 617–631 (2015).

    PubMed  Google Scholar 

  58. Mitchell, J. F. & Leopold, D. A. The marmoset monkey as a model for visual neuroscience. Neurosci. Res. 93, 20–46 (2015).

    PubMed  PubMed Central  Google Scholar 

  59. Sahel, J.-A. & Roska, B. Gene therapy for blindness. Annu. Rev. Neurosci. 36, 467–488 (2013).

    CAS  PubMed  Google Scholar 

  60. Carter, B. J. Adeno-associated virus and the development of adeno-associated virus vectors: a historical perspective. Mol. Ther. 10, 981–989 (2004).

    CAS  PubMed  Google Scholar 

  61. Ali, R. R. et al. Gene transfer into the mouse retina mediated by an adeno-associated viral vector. Hum. Mol. Genet. 5, 591–594 (1996).The first AAV gene transfer to the retina of mice.

    CAS  PubMed  Google Scholar 

  62. Flannery, J. G. et al. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc. Natl Acad. Sci. USA 94, 6916–6921 (1997).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  63. Planul, A. & Dalkara, D. Vectors and gene delivery to the retina. Annu. Rev. Vis. Sci. 3, 121–140 (2017).

    PubMed  Google Scholar 

  64. Madigan, V. J. & Asokan, A. Engineering AAV receptor footprints for gene therapy. Curr. Opin. Virol. 18, 89–96 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Chaffiol, A. et al. A new promoter allows optogenetic vision restoration with enhanced sensitivity in macaque retina. Mol. Ther. 25, 2546–2560 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Jacobson, S. G. et al. Gene therapy for Leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch. Ophthalmol. 130, 9–24 (2012).

    CAS  PubMed  Google Scholar 

  67. Wang, S. et al. Non-invasive, focused ultrasound-facilitated gene delivery for optogenetics. Sci. Rep. 7, 39955 (2017).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wan, C., Li, F. & Li, H. Gene therapy for ocular diseases meditated by ultrasound and microbubbles. Mol. Med. Rep. 12, 4803–4814 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Touchard, E. et al. Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose. Gene Ther. 19, 886–898 (2012).

    CAS  PubMed  Google Scholar 

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

    ADS  CAS  PubMed  Google Scholar 

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  72. MacLaren, R. E. Cone fusion confusion in photoreceptor transplantation. Stem Cell Investig. 4, 71 (2017).

    PubMed  PubMed Central  Google Scholar 

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  74. 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).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hertz, J. et al. Survival and integration of developing and progenitor-derived retinal ganglion cells following transplantation. Cell Transplant. 23, 855–872 (2014).

    PubMed  Google Scholar 

  77. Venugopalan, P. et al. Transplanted neurons integrate into adult retinas and respond to light. Nat. Commun. 7, 10472 (2016).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sahel, J. A. et al. Mitogenic effects of excitatory amino acids in the adult rat retina. Exp. Eye Res. 53, 657–664 (1991).

    CAS  PubMed  Google Scholar 

  79. Jorstad, N. L. et al. Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature 548, 103–107 (2017).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  80. Benowitz, L. & Yin, Y. Rewiring the injured CNS: lessons from the optic nerve. Exp. Neurol. 209, 389–398 (2008).

    CAS  PubMed  Google Scholar 

  81. Lim, J.-H. A. et al. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat. Neurosci. 19, 1073–1084 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Sun, F. et al. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature 480, 372–375 (2011).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  83. Laha, B., Stafford, B. K. & Huberman, A. D. Regenerating optic pathways from the eye to the brain. Science 356, 1031–1034 (2017).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  84. Yue, L., Weiland, J. D., Roska, B. & Humayun, M. S. Retinal stimulation strategies to restore vision: fundamentals and systems. Prog. Retin. Eye Res. 53, 21–47 (2016).

    PubMed  Google Scholar 

  85. Scholl, H. P. N. et al. Emerging therapies for inherited retinal degeneration. Sci. Transl. Med. 8, 368rv6 (2016).

    PubMed  Google Scholar 

  86. 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 

  87. Stronks, H. C. & Dagnelie, G. The functional performance of the Argus II retinal prosthesis. Expert Rev. Med. Devices 11, 23–30 (2014).

    CAS  PubMed  Google Scholar 

  88. Mullin, E. A company is reviving efforts to make a bionic eye brain implant for the blind. MIT Technol. Rev. https://www.technologyreview.com/s/608844/blind-patients-to-test-bionic-eye-brain-implants/ (2017).

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

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 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).

    CAS  PubMed  Google Scholar 

  91. Polosukhina, A. et al. Photochemical restoration of visual responses in blind mice. Neuron 75, 271–282 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Busskamp, V., Picaud, S., Sahel, J. A. & Roska, B. Optogenetic therapy for retinitis pigmentosa. Gene Ther. 19, 169–175 (2012).

    CAS  PubMed  Google Scholar 

  93. Berndt, A., Yizhar, O., Gunaydin, L. A., Hegemann, P. & Deisseroth, K. Bi-stable neural state switches. Nat. Neurosci. 12, 229–234 (2009).

    CAS  PubMed  Google Scholar 

  94. Hartong, D. T., Berson, E. L. & Dryja, T. P. Retinitis pigmentosa. Lancet 368, 1795–1809 (2006).

    CAS  PubMed  Google Scholar 

  95. den Hollander, A. I., Roepman, R., Koenekoop, R. K. & Cremers, F. P. M. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog. Retin. Eye Res. 27, 391–419 (2008).

    Google Scholar 

  96. 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).

    ADS  CAS  PubMed  Google Scholar 

  97. Bourne, D. et al. Whole-eye transplantation: a look into the past and vision for the future. Eye (Lond.) 31, 179–184 (2017).

    CAS  Google Scholar 

  98. Miller, J. W. Beyond VEGF—the Weisenfeld lecture. Invest. Ophthalmol. Vis. Sci. 57, 6911–6918 (2016).

    PubMed  PubMed Central  Google Scholar 

  99. 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).

    CAS  PubMed  Google Scholar 

  100. Parker, M. A. et al. Test–retest variability of functional and structural parameters in patients with Stargardt disease participating in the SAR422459 gene therapy trial. Transl. Vis. Sci. Technol. 5, 10 (2016).

    PubMed  PubMed Central  Google Scholar 

  101. Byrne, L. C. et al. Viral-mediated RdCVF and RdCVFL expression protects cone and rod photoreceptors in retinal degeneration. J. Clin. Invest. 125, 105–116 (2015).

    PubMed  Google Scholar 

  102. Léveillard, T. et al. Identification and characterization of rod-derived cone viability factor. Nat. Genet. 36, 755–759 (2004).Discovery of a factor for photoreceptor neuroprotection.

    PubMed  Google Scholar 

  103. Mohand-Said, S. et al. Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse. Proc. Natl Acad. Sci. USA 95, 8357–8362 (1998).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  104. Aït-Ali, N. et al. Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis. Cell 161, 817–832 (2015).

    PubMed  Google Scholar 

  105. Venkatesh, A. et al. Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice. J. Clin. Invest. 125, 1446–1458 (2015).

    PubMed  PubMed Central  Google Scholar 

  106. Punzo, C., Kornacker, K. & Cepko, C. L. Stimulation of the insulin/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa. Nat. Neurosci. 12, 44–52 (2009).Discovery of a factor for photoreceptor neuroprotection.

    CAS  PubMed  Google Scholar 

  107. Xiong, W., MacColl Garfinkel, A. E., Li, Y., Benowitz, L. I. & Cepko, C. L. NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage. J. Clin. Invest. 125, 1433–1445 (2015).

    PubMed  PubMed Central  Google Scholar 

  108. Cepko, C. & Punzo, C. Cell metabolism: sugar for sight. Nature 522, 428–429 (2015).

    ADS  CAS  PubMed  Google Scholar 

  109. Krol, J. & Roska, B. Rods feed cones to keep them alive. Cell 161, 706–708 (2015).

    CAS  PubMed  Google Scholar 

  110. Léveillard, T. & Sahel, J.-A. Metabolic and redox signaling in the retina. Cell. Mol. Life Sci. 74, 3649–3665 (2016).

    PubMed  PubMed Central  Google Scholar 

  111. Campochiaro, P. A. et al. Is there excess oxidative stress and damage in eyes of patients with retinitis pigmentosa? Antioxid. Redox Signal. 23, 643–648 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Kayser, S. et al. Reduced central retinal artery blood flow is related to impaired central visual function in retinitis pigmentosa patients. Curr. Eye Res. 42, 1503–1510 (2017).

    PubMed  PubMed Central  Google Scholar 

  113. Chaikin, L., Kashiwa, K., Bennet, M., Papastergiou, G. & Gregory, W. Microcurrent stimulation in the treatment of dry and wet macular degeneration. Clin. Ophthalmol. 9, 2345–2353 (2015).

    PubMed  PubMed Central  Google Scholar 

  114. Schatz, A. et al. Transcorneal electrical stimulation for patients with retinitis pigmentosa: a prospective, randomized, sham-controlled follow-up study over 1 year. Invest. Ophthalmol. Vis. Sci. 58, 257–269 (2017).

    PubMed  Google Scholar 

  115. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol. 119, 1417–1436 (2001).

    Google Scholar 

  116. Jurkute, N. & Yu-Wai-Man, P. Leber hereditary optic neuropathy: bridging the translational gap. Curr. Opin. Ophthalmol. 28, 403–409 (2017).

    PubMed  PubMed Central  Google Scholar 

  117. Smirnakis, S. M. Probing human visual deficits with functional magnetic resonance imaging. Annu. Rev. Vis. Sci. 2, 171–195 (2016).

    PubMed  PubMed Central  Google Scholar 

  118. Bainbridge, J. W. B. et al. Long-term effect of gene therapy on Leber’s congenital amaurosis. N. Engl. J. Med. 372, 1887–1897 (2015).

    PubMed  PubMed Central  Google Scholar 

  119. Jacobson, S. G. et al. Improvement and decline in vision with gene therapy in childhood blindness. N. Engl. J. Med. 372, 1920–1926 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Rizzo, J. F. III & Ayton, L. N. Psychophysical testing of visual prosthetic devices: a call to establish a multi-national joint task force. J. Neural Eng. 11, 020301 (2014).

    ADS  PubMed  Google Scholar 

  121. Finger, R. P. et al. Developing the impact of Vision Impairment-Very Low Vision (IVI-VLV) questionnaire as part of the LoVADA protocol. Invest. Ophthalmol. Vis. Sci. 55, 6150–6158 (2014).

    PubMed  Google Scholar 

  122. Jeter, P. E., Rozanski, C., Massof, R., Adeyemo, O. & Dagnelie, G. Development of the Ultra-Low Vision Visual Functioning Questionnaire (ULV-VFQ). Transl. Vis. Sci. Technol. 6, 11 (2017).

    PubMed  PubMed Central  Google Scholar 

  123. Authié, C. N., Berthoz, A., Sahel, J.-A. & Safran, A. B. Adaptive gaze strategies for locomotion with constricted visual field. Front. Hum. Neurosci. 11, 387 (2017).

    PubMed  PubMed Central  Google Scholar 

  124. Cattaneo, Z. & Vecchi, T. Blind Vision (MIT Press, Cambridge, 2011).

  125. Irvine, D. et al. Tablet and smartphone accessibility features in the low vision rehabilitation. Neuroophthalmology 38, 53–59 (2014).

    PubMed  PubMed Central  Google Scholar 

  126. Robinson, J. L., Braimah Avery, V., Chun, R., Pusateri, G. & Jay, W. M. Usage of accessibility options for the iPhone and iPad in a visually impaired population. Semin. Ophthalmol. 32, 163–171 (2017).

    PubMed  Google Scholar 

  127. Alter, C. Facebook is developing technology that can describe pictures to blind people. Time http://time.com/4099204/facebook-artificial-intelligence-blind-pictures/ (2015).

  128. Striem-Amit, E., Guendelman, M. & Amedi, A. ‘Visual’ acuity of the congenitally blind using visual-to-auditory sensory substitution. PLoS One 7, e33136 (2012).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  129. Striem-Amit, E., Cohen, L., Dehaene, S. & Amedi, A. Reading with sounds: sensory substitution selectively activates the visual word form area in the blind. Neuron 76, 640–652 (2012).

    CAS  PubMed  Google Scholar 

  130. Thaler, L. & Goodale, M. A. Echolocation in humans: an overview. Wiley Interdiscip. Rev. Cogn. Sci. 7, 382–393 (2016).

    PubMed  Google Scholar 

  131. Köberlein, J., Beifus, K., Schaffert, C. & Finger, R. P. The economic burden of visual impairment and blindness: a systematic review. BMJ Open 3, e003471 (2013).

    PubMed  PubMed Central  Google Scholar 

  132. Romanov, R. A. et al. Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes. Nat. Neurosci. 20, 176–188 (2017).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank S. Trenholm for discussions, comments and advice on the manuscript; A. Drinnenberg, D. Dalkara, S. Picaud, I. Audo, K. Marazova, S. Oakeley and P. King for comments on the manuscript; and P. Maloca for images for Fig. 1, A. Drinnenberg for drawings for Fig. 2, and V. Juvin (http://www.sciartwork.com) for images for Fig. 3.

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Nature thanks G. Dagnelie, J. Demb and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland

    Botond Roska

  2. Neural Circuit Laboratories, Friedrich Miescher Institute, Basel, Switzerland

    Botond Roska

  3. Department of Ophthalmology, University of Basel, Basel, Switzerland

    Botond Roska

  4. Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    José-Alain Sahel

  5. Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France

    José-Alain Sahel

  6. CHNO des Quinze-Vingts, CIC INSERM-DGOS 1423, DHU Sight Restore, Paris, France

    José-Alain Sahel

  7. Department of Ophthalmology, Fondation Ophtalmologique Rothschild, Paris, France

    José-Alain Sahel

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  1. Botond Roska
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  2. José-Alain Sahel
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Contributions

B.R. and J.A.-S. discussed and wrote the manuscript.

Corresponding authors

Correspondence to Botond Roska or José-Alain Sahel.

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Competing interests

J.A.-S. has financial interests in GenSight Biologics, Chronocam, Chronolife, Pixium Vision, Tilak Healthcare, and Sparing Vision.

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Roska, B., Sahel, JA. Restoring vision. Nature 557, 359–367 (2018). https://doi.org/10.1038/s41586-018-0076-4

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