De Silva, S., Barnard, A., Hughes, S. et al. (9 more authors) (2017) Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy. Proceedings of the National Academy of Sciences, 114 (42). pp. 11211-11216. ISSN 1091-6490
Abstract
Optogenetic strategies to restore vision in patients who are blind from end-stage retinal degenerations aim to render remaining retinal cells light sensitive once photoreceptors are lost. Here, we assessed long-term functional outcomes following subretinal delivery of the human melanopsin gene (OPN4) in the rd1 mouse model of retinal degeneration using an adeno-associated viral vector. Ectopic expression of OPN4 using a ubiquitous promoter resulted in cellular depolarization and ganglion cell action potential firing. Restoration of the pupil light reflex, behavioral light avoidance, and the ability to perform a task requiring basic image recognition were restored up to 13 mo following injection. These data suggest that melanopsin gene therapy via a subretinal route may be a viable and stable therapeutic option for the treatment of end-stage retinal degeneration in humans.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 PNAS. |
Keywords: | human melanopsin; gene therapy; optogenetics |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) |
Funding Information: | Funder Grant number ROYAL SOCIETY UF080113 ROYAL SOCIETY UF130327 WELLCOME TRUST (THE) 093223/B/10/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Oct 2017 11:19 |
Last Modified: | 14 Nov 2017 13:52 |
Published Version: | https://doi.org/10.1073/pnas.1701589114 |
Status: | Published |
Publisher: | National Academy of Sciences |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.1701589114 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:122342 |