TY - JOUR
T1 - Photochemical Restoration of Visual Responses in Blind Mice
AU - Polosukhina, Aleksandra
AU - Litt, Jeffrey
AU - Tochitsky, Ivan
AU - Nemargut, Joseph
AU - Sychev, Yivgeny
AU - De Kouchkovsky, Ivan
AU - Huang, Tracy
AU - Borges, Katharine
AU - Trauner, Dirk
AU - Van Gelder, Russell N.
AU - Kramer, Richard H.
N1 - Funding Information:
We thank A. Anishchenko and J. Elstrott for helpful comments and discussions; Trevor Lee, Andrew Noblet, R. Montpetit, T. Lamprecht, and X. Qiu for technical and experimental assistance; and J. Flannery and K. Greenberg for valuable suggestions. This work was supported by the National Eye Institute (NEI), which provided research Grant EY018957 to R.H.K., Core Grant P30 EY003176 to R.H.K., and Core Grant P30 EY001730 to R.V.G. This work was also supported by Beckman Foundation for Macular Research (R.H.K.) and a Research to Prevent Blindness award to Y.S. and R.V.G. and an Ezell Fellowship to A.P. The NEI also funded the Nanomedicine Development Center (PN2 EY018241), which supported this interdisciplinary project. R.H.K. and D.T. are SAB members and consultants of Photoswitch Bioscience, Inc., which is developing commercial uses for chemical photoswitches. A.P., J.L., I.T., J.N., Y.S., T.H., I.D.K., and K.B. conducted the in vitro and in vivo experiments. D.T. designed and synthesized chemical reagents. R.H.K. and R.V.G. coordinated the research and wrote the manuscript. R.H.K. initiated the research and supervised the program.
PY - 2012/7/26
Y1 - 2012/7/26
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2012.05.022
DO - 10.1016/j.neuron.2012.05.022
M3 - Article
C2 - 22841312
AN - SCOPUS:84864317757
SN - 0896-6273
VL - 75
SP - 271
EP - 282
JO - Neuron
JF - Neuron
IS - 2
ER -