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
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Copyright, Publisher and Additional Information: | © 2017 PNAS. | ||||||||
Keywords: | human melanopsin; gene therapy; optogenetics | ||||||||
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Institution: | The University of Sheffield | ||||||||
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) | ||||||||
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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: | https://doi.org/10.1073/pnas.1701589114 | ||||||||
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