Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11211-11216. doi: 10.1073/pnas.1701589114. Epub 2017 Oct 2.

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

Author information

1
Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, National Institute for Health Research Biomedical Research Centre, Oxford OX3 9DU, United Kingdom.
2
Department of Psychology, The University of Sheffield, Sheffield S1 2LT, United Kingdom.
3
The Ohio State University, Columbus, OH 43210.
4
Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, National Institute for Health Research Biomedical Research Centre, Oxford OX3 9DU, United Kingdom; mark.hankins@eye.ox.ac.uk enquiries@eye.ox.ac.uk.
5
Moorfields Eye Hospital, National Institute for Health Research Biomedical Research Centre, London EC1V 2PD, United Kingdom.

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.

KEYWORDS:

gene therapy; human melanopsin; optogenetics

PMID:
28973921
PMCID:
PMC5651734
DOI:
10.1073/pnas.1701589114
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict of interest statement: S.R.D.S., A.R.B., M.W.H., and R.E.M. are listed as inventors on a patent submitted by the University of Oxford relevant to this work. R.E.M. is a founding director of Nightstarx Ltd., a retinal gene therapy company established by the University of Oxford and owned by the Wellcome Trust. M.W.H. is listed as an inventor on a patent owned by Imperial College London relating to restoring light responses by ectopic expression of melanopsin.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center