Restoration of vision with ectopic expression of human rod opsin
Open accessAbstract
Many retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically expressed human rod opsin, driven by either a non-selective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice. These responses could be elicited at light intensities within the physiological range and substantially below those required by other optogenetic strategies. Mice with rod opsin expression driven by the ON-bipolar specific promoter displayed behavioral responses to increases in luminance, flicker, coarse spatial patterns, and elements of a natural movie at levels of contrast and illuminance (≈50-100 lux) typical of natural indoor environments. These data reveal that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities. Given the inherent advantages in employing a human protein, the simplicity of this intervention, and the quality of vision restored, we suggest that rod opsin merits consideration as an optogenetic actuator for treating patients with advanced retinal degeneration.
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Pre-clinical optogenetic trials in mouse models of retinitis pigmentosa have restored basic visual function in blind animals, providing proof of principle.
“Pre-clinical trials of optogenic therapies in murine models of retinitis pigmentosa have provided proof-of-principle in restoring basic visual function to blind animals, and human clinical trials are currently underway.”
From Correcting visual loss by genetics and prosthetics (2020) · cites this paper as Cehajic-Kapetanovic 2015
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- Authors
- Cehajic-Kapetanovic, J., Eleftheriou, C., Allen, A. E., Milosavljevic, N., Pienaar, A., Bedford, R., Davis, K. E., Bishop, P. N., & Lucas, R. J.
- Affiliations
- University of Manchester (GB)
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Bishop, Paul N.
- Lucas, Robert J.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 25
- Issue
- 16
- Pages
- 2111-2122
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC4540256
- OpenAlex
- W1602094372
- Cited by
- 184
- References
- 36
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 10 · 2023: 22 · 2022: 31 · 2021: 18 · 2020: 18 · 2019: 21 · 2018: 9 · 2017: 19 · 2016: 9 · 2015: 3
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Current Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Medical Research Council (MC_PC_13070)
- Biotechnology and Biological Sciences Research Council (BB/K002252/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- rod opsin, optogenetics, retinal degeneration, retinal dystrophy, ectopic expression, ON bipolar cells, photoreceptor loss, vision restoration, viral gene delivery, retinal explants, visual thalamus, photosensitivity, mouse model
- MeSH terms
- Ectopic Gene Expression, Animals, Humans, Retinal Degeneration, Rhodopsin, Mice
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