Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy

Samantha R. De Silva; Alun R. Barnard; Steven Hughes; Shu K.E. Tam; Chris Martin; Mandeep S. Singh; Alona O. Barnea-Cramer; Michelle E. McClements; Matthew J. During; Stuart N. Peirson; Mark W. Hankins; Robert E. MacLaren

doi:10.1073/pnas.1701589114

Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy

Samantha R. De Silva, Alun R. Barnard, Steven Hughes, Shu K.E. Tam, Chris Martin, Mandeep S. Singh, Alona O. Barnea-Cramer, Michelle E. McClements, Matthew J. During, Stuart N. Peirson, Mark W. Hankins, Robert E. MacLaren

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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.

Original language	English (US)
Pages (from-to)	11211-11216
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	42
DOIs	https://doi.org/10.1073/pnas.1701589114
State	Published - Oct 17 2017
Externally published	Yes

Keywords

Gene therapy
Human melanopsin
Optogenetics

ASJC Scopus subject areas

General

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10.1073/pnas.1701589114

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De Silva, S. R., Barnard, A. R., Hughes, S., Tam, S. K. E., Martin, C., Singh, M. S., Barnea-Cramer, A. O., McClements, M. E., During, M. J., Peirson, S. N., Hankins, M. W., & MacLaren, R. E. (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 of the United States of America, 114(42), 11211-11216. https://doi.org/10.1073/pnas.1701589114

Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy. / De Silva, Samantha R.; Barnard, Alun R.; Hughes, Steven et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 42, 17.10.2017, p. 11211-11216.

Research output: Contribution to journal › Article › peer-review

De Silva, SR, Barnard, AR, Hughes, S, Tam, SKE, Martin, C, Singh, MS, Barnea-Cramer, AO, McClements, ME, During, MJ, Peirson, SN, Hankins, MW & MacLaren, RE 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 of the United States of America, vol. 114, no. 42, pp. 11211-11216. https://doi.org/10.1073/pnas.1701589114

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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.",

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N1 - Funding Information: ACKNOWLEDGMENTS. Funding was provided by Wellcome Trust, National Institute for Health Research Biomedical Research Centres of Oxford and Moorfields, Medical Research Council, Biotechnology and Biological Sciences Research Council, and Royal College of Surgeons of Edinburgh. Publisher Copyright: © 2017, National Academy of Sciences. All rights reserved.

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Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy

Abstract

Keywords

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