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

Journal article

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 adenoassociated viral vector. Ectopic expression of OPN4 using a ubiquitous promoter resulted in cellular depolarisation and ganglion cell action potential firing. Restoration of the pupil light reflex, behavioural light avoidance and the ability to perform a task requiring basic image recognition were restored up to 13 months 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.

Authors: De Silva, SR; Barnard, AR; Hughes, S; Tam, SKE; Martin, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: National Academy of Sciences
• Journal: Proceedings of the National Academy of Sciences
• Volume: 114
• Issue: 42
• Pages: 11211–11216
• Publication date: 2017-10-02
• Acceptance date: 2017-08-29
• DOI: 10.1073/pnas.1701589114
• ISSN: 1091-6490
• Keywords: optogenetics; gene therapy; human melanopsin