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

First Author  Tochitsky I Year  2014
Journal  Neuron Volume  81
Issue  4 Pages  800-13
PubMed ID  24559673 Mgi Jnum  J:220643
Mgi Id  MGI:5635768 Doi  10.1016/j.neuron.2014.01.003
Citation  Tochitsky I, et al. (2014) Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells. Neuron 81(4):800-13
abstractText  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.
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