Photochemical Restoration of Visual Responses in Blind Mice

Aleksandra Polosukhina, Jeffrey Litt, Ivan Tochitsky, Joseph Nemargut, Yivgeny Sychev, Ivan De Kouchkovsky, Tracy Huang, Katharine Borges, Dirk Trauner, Russell N. Van Gelder, Richard H. Kramer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)271-282
Number of pages12
JournalNeuron
Volume75
Issue number2
DOIs
StatePublished - Jul 26 2012

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Light
Photophobia
Vertebrate Photoreceptor Cells
Retinitis Pigmentosa
Pupillary Reflex
Intraocular Injections
Avoidance Learning
Retinal Neurons
Retinal Ganglion Cells
Macular Degeneration
Retina
Brain
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Polosukhina, A., Litt, J., Tochitsky, I., Nemargut, J., Sychev, Y., De Kouchkovsky, I., ... Kramer, R. H. (2012). Photochemical Restoration of Visual Responses in Blind Mice. Neuron, 75(2), 271-282. https://doi.org/10.1016/j.neuron.2012.05.022

Photochemical Restoration of Visual Responses in Blind Mice. / Polosukhina, Aleksandra; Litt, Jeffrey; Tochitsky, Ivan; Nemargut, Joseph; Sychev, Yivgeny; De Kouchkovsky, Ivan; Huang, Tracy; Borges, Katharine; Trauner, Dirk; Van Gelder, Russell N.; Kramer, Richard H.

In: Neuron, Vol. 75, No. 2, 26.07.2012, p. 271-282.

Research output: Contribution to journalArticle

Polosukhina, A, Litt, J, Tochitsky, I, Nemargut, J, Sychev, Y, De Kouchkovsky, I, Huang, T, Borges, K, Trauner, D, Van Gelder, RN & Kramer, RH 2012, 'Photochemical Restoration of Visual Responses in Blind Mice', Neuron, vol. 75, no. 2, pp. 271-282. https://doi.org/10.1016/j.neuron.2012.05.022
Polosukhina A, Litt J, Tochitsky I, Nemargut J, Sychev Y, De Kouchkovsky I et al. Photochemical Restoration of Visual Responses in Blind Mice. Neuron. 2012 Jul 26;75(2):271-282. https://doi.org/10.1016/j.neuron.2012.05.022
Polosukhina, Aleksandra ; Litt, Jeffrey ; Tochitsky, Ivan ; Nemargut, Joseph ; Sychev, Yivgeny ; De Kouchkovsky, Ivan ; Huang, Tracy ; Borges, Katharine ; Trauner, Dirk ; Van Gelder, Russell N. ; Kramer, Richard H. / Photochemical Restoration of Visual Responses in Blind Mice. In: Neuron. 2012 ; Vol. 75, No. 2. pp. 271-282.
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