title: Photochemical restoration of visual responses in blind mice.
abstract: Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are degenerative blinding diseases caused by the death of rods and cones, leaving the remainder of the visual system intact but largely unable to respond to light. Here, we show that AAQ, a synthetic small molecule photoswitch, can restore light sensitivity to the retina and behavioral responses in vivo in mouse models of RP, without exogenous gene delivery. Brief application of AAQ bestows prolonged light sensitivity on multiple types of retinal neurons, resulting in synaptically amplified responses and center-surround antagonism in arrays of retinal ganglion cells (RGCs). Intraocular injection of AAQ restores the pupillary light reflex and locomotory light avoidance behavior in mice lacking retinal photoreceptors, indicating reconstitution of light signaling to brain circuits. AAQ and related photoswitch molecules present a potential drug strategy for restoring retinal function in degenerative blinding diseases.
authors: Vision Science Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Aleksandra
authors: A
authors: Polosukhina
authors: Jeffrey
authors: J
authors: Litt
authors: Ivan
authors: I
authors: Tochitsky
authors: Joseph
authors: J
authors: Nemargut
authors: Yivgeny
authors: Y
authors: Sychev
authors: Ivan
authors: I
authors: De Kouchkovsky
authors: Tracy
authors: T
authors: Huang
authors: Katharine
authors: K
authors: Borges
authors: Dirk
authors: D
authors: Trauner
authors: Russell N
authors: RN
authors: Van Gelder
authors: Richard H
authors: RH
authors: Kramer
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001766:Blindness / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D051379:Mice; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D055351:Retinal Neurons / Q000187:drug effects* / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D001391:Azo Compounds; D017319:Photosensitizing Agents; D000644:Quaternary Ammonium Compounds; C009850:azobenzene