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

Ivan Tochitsky, Aleksandra Polosukhina, Vadim E. Degtyar, Nicholas Gallerani, Caleb M. Smith, Aaron Friedman, Russell N. Van Gelder, Dirk Trauner, Daniela Kaufer, Richard H. Kramer

Research output: Contribution to journalArticlepeer-review

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 iseffective 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.

Original languageEnglish (US)
Pages (from-to)800-813
Number of pages14
JournalNeuron
Volume81
Issue number4
DOIs
StatePublished - Feb 19 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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