Photochemical Restoration of Visual Responses in Blind Mice

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. ► Photochemical molecule (AAQ) restores light sensitivity to retinas from blind mice ► AAQ-mediated photosensitization occurs quickly and requires no genetic modification ► AAQ acts on many retinal cell types, amplifying and shaping the RGC light response ► Intraocular AAQ injection restores light-elicited behavior in vivo in blind mice The most common blinding diseases are caused by degeneration of rods and cones in the retina. Polosukhina et al. show that a photoswitch molecule imparts light sensitivity to the retina of blind mice, restoring light elicited behavior in-vivo.