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 journalArticle

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 languageEnglish (US)
Pages (from-to)11211-11216
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number42
DOIs
StatePublished - Oct 17 2017

Keywords

  • Gene therapy
  • Human melanopsin
  • Optogenetics

ASJC Scopus subject areas

  • General

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