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Neuron. 2014 Feb 19;81(4):800-13. doi: 10.1016/j.neuron.2014.01.003.

Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells.

Author information

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • 2Vision Science Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
  • 3Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • 4Departments of Ophthalmology, Pathology, and Biological Structure, University of Washington, Seattle, WA 98195, USA.
  • 5Department of Chemistry and Biochemistry, University of Munich, 81377 Munich, Germany.
  • 6Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neurosciences Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • 7Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Vision Science Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neurosciences Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: rhkramer@berkeley.edu.

Abstract

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. Here, we report a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight. A single intraocular injection of DENAQ photosensitizes the blind retina for days, restoring electrophysiological and behavioral responses with no toxicity. Experiments on mouse strains with functional, nonfunctional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated photoreceptors. DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing. The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
24559673
[PubMed - indexed for MEDLINE]
PMCID:
PMC3933823
Free PMC Article
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