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

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


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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dependovirus
  • Disease Models, Animal
  • Genetic Therapy / methods*
  • Humans
  • Mice, Inbred C3H
  • Retinal Degeneration / therapy*
  • Rod Opsins / genetics*
  • Vision, Ocular


  • Rod Opsins
  • melanopsin