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Bioengineering strategies for restoring vision

Nature Biomedical Engineering volume 7, pages 387–404 (2023)Cite this article

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Abstract

Late-stage retinal degenerative disease involving photoreceptor loss can be treated by optogenetic therapy, cell transplantation and retinal prostheses. These approaches aim to restore light sensitivity to the retina as well as visual perception by integrating neuronal responses for transmission to the cortex. In age-related macular degeneration, some cell-based therapies also aim to restore photoreceptor-supporting tissue to prevent complete photoreceptor loss. In the earlier stages of degeneration, gene-replacement therapy could attenuate retinal-disease progression and reverse loss of function. And gene-editing strategies aim to correct the underlying genetic defects. In this Review, we highlight the most promising gene therapies, cell therapies and retinal prostheses for the treatment of retinal disease, discuss the benefits and drawbacks of each treatment strategy and the factors influencing whether functional tissue is reconstructed and repaired or replaced with an electronic device, and summarize upcoming technologies for enhancing the restoration of vision.

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Fig. 1: Treatments in vision restoration according to retinal-degeneration stage, and structural remodelling in typical rod–cone dystrophy.
Fig. 2: Normal retinal phenotype and three different types of retinal degeneration.
Fig. 3: Delivery of human rhodopsin in rd1 mice via an AAV vector using a ubiquitous chicken-β-actin promoter.
Fig. 4: Subretinal transplantation of Nrl–GFP donor cells into rd1–DsRed mice with advanced photoreceptor-layer atrophy.
Fig. 5: The visual pathway and locations of different retinal implants147.
Fig. 6: Electronic subretinal implant.

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Acknowledgements

We thank J. Brett (BA Arts and Graphics) and T. Buckley (BM BCh) from Eye Research Group Oxford for their help with the images and figure design. We acknowledge funding from the University of Oxford NIHR Biomedical Research Centre. J.C.-K. was also funded by the Global Ophthalmology Fellowship Awards Programme, Bayer, Switzerland. E.Z. was supported by the DFG excellence center EXC 307 (CIN Tübingen). R.E.M. was funded by an MRC i4i Award for clinical trials of retinal implants.

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Authors and Affiliations

  1. Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK

    Jasmina Cehajic-Kapetanovic & Robert E. MacLaren

  2. Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

    Jasmina Cehajic-Kapetanovic & Robert E. MacLaren

  3. Johns Hopkins Medical Institute, Baltimore, MD, USA

    Mandeep S. Singh

  4. Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany

    Eberhart Zrenner

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  1. Jasmina Cehajic-Kapetanovic
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  4. Robert E. MacLaren
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J.C.-K. wrote and revised the manuscript, with input from E.Z. on section ‘Retinal and cortical prostheses’, M.S.S. on section ‘Cell therapy’, and R.E.M. on the overall manuscript. All authors approved the final version of the manuscript.

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Correspondence to Jasmina Cehajic-Kapetanovic.

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Cehajic-Kapetanovic, J., Singh, M.S., Zrenner, E. et al. Bioengineering strategies for restoring vision. Nat. Biomed. Eng 7, 387–404 (2023). https://doi.org/10.1038/s41551-021-00836-4

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