March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Restoring Photosensitivity In Blind Mice With Small Molecular Photoswitch Phenyl-ethyl Aniline Azobenzene Quaternary Ammonium
Author Affiliations & Notes
  • Joseph P. Nemargut, III
    Ophthalmology, University of Washington, Seattle, Washington
  • Scott Greenwald
    Ophthalmology, University of Washington, Seattle, Washington
  • Lauren Rotkis
    Ophthalmology, University of Washington, Seattle, Washington
  • Richard H. Kramer
    Molecular and Cell Biology, University of California, Berkeley, Berkeley, California
  • Dirk Trauner
    Chemistry and Biochemistry, Ludwig Maximilians University, Munich, Germany
  • Russell N. Van Gelder
    Ophthalmology, University of Washington, Seattle, Washington
  • Footnotes
    Commercial Relationships  Joseph P. Nemargut, III, None; Scott Greenwald, None; Lauren Rotkis, None; Richard H. Kramer, None; Dirk Trauner, None; Russell N. Van Gelder, None
  • Footnotes
    Support  NIH Grant EY14988, NDC Nano Grant 2PN2EY018241-06
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3639. doi:
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      Joseph P. Nemargut, III, Scott Greenwald, Lauren Rotkis, Richard H. Kramer, Dirk Trauner, Russell N. Van Gelder; Restoring Photosensitivity In Blind Mice With Small Molecular Photoswitch Phenyl-ethyl Aniline Azobenzene Quaternary Ammonium. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3639.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Small molecular photoswitches bind to endogenous ion channels in neurons and change their activity in response to light. They may be therapeutically valuable in treating retinitis pigmentosa or macular degeneration by conferring photosensitivity on retinal ganglion cells in the absence of classical photoreceptors. In this study, we used small molecular photoswitch, phenyl-ethyl aniline azobenzene quaternary ammonium (PhENAQ), to restore light sensitivity in retinas from adult blind mice without involving exogenous gene delivery.

Methods: : Exp1. Following brief application of PhENAQ, the light responses from adult Opn4-/-;rd/rd blind mouse retinal explants were recorded on multi-electrode arrays. We analyzed the light-triggered firing of ganglion cells exposed to several wavelengths and intensities of light. Exp2. In vivo testing was performed by injecting PhENAQ intravitreally into Opn4-/-;rd/rd mice. The visually-guided behavior was recorded from the mice pre- and post-injection with open-field and OptoMotry experiments. Additionally, the pupillary light reflex and electroretinograms from these mice were evaluated. The mice injected with PhENAQ were compared to both wildtype and sham-injected Opn4-/-;rd/rd mice.

Results: : PhENAQ bestowed light sensitivity onto blind mouse retinal explants, which responded optimally to broad-spectrum white or blue light. Typically, the light increased ganglion cell firing in <1 sec, with rapid cessation in the dark. The robust light responses persisted for hours after washout of PhENAQ from the extracellular solution. In vivo experiments indicate that a single injection of PhENAQ is sufficient to restore some light-dependent behaviors in blind mice.

Conclusions: : Application of PhENAQ to rd/rd retinas confers light sensitivity in vitro and in vivo, with desirable spectral and kinetic properties for a potential therapeutic agent.

Keywords: retinal degenerations: cell biology • retina: proximal (bipolar, amacrine, and ganglion cells) • visual acuity 
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