Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

Carey Y L Huh; Henri Leinonen; Taylor Nakayama; Julia R Tomasello; Jianye Zhang; Jack Zeitoun; John P Peach; Maximilian Halabi; Jianying Z Kiser; Krzysztof Palczewski; Philip D Kiser; Sunil P Gandhi

doi:10.1016/j.cub.2022.09.005

Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

Curr Biol. 2022 Oct 24;32(20):4538-4546.e5. doi: 10.1016/j.cub.2022.09.005. Epub 2022 Sep 23.

Authors

Affiliations

¹ Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA.
² Gavin Herbert Eye Institute, Department of Ophthalmology, Center for Translational Vision Research, University of California, Irvine, Irvine, CA 92697, USA; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio 70211, Finland.
³ Gavin Herbert Eye Institute, Department of Ophthalmology, Center for Translational Vision Research, University of California, Irvine, Irvine, CA 92697, USA.
⁴ Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
⁵ Gavin Herbert Eye Institute, Department of Ophthalmology, Center for Translational Vision Research, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92697, USA.
⁶ Gavin Herbert Eye Institute, Department of Ophthalmology, Center for Translational Vision Research, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Department of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
⁷ Gavin Herbert Eye Institute, Department of Ophthalmology, Center for Translational Vision Research, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Research Service, VA Long Beach Healthcare System, Long Beach, CA 90822, USA; Department of Clinical Pharmacy Practice, University of California, Irvine, Irvine, CA 92697, USA.
⁸ Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: spgandhi@uci.edu.

Abstract

Despite the recent emergence of multiple cellular and molecular strategies to restore vision in retinal disorders, it remains unclear to what extent central visual circuits can recover when retinal defects are corrected in adulthood. We addressed this question in an Lrat^-/- mouse model of Leber congenital amaurosis (LCA) in which retinal light sensitivity and optomotor responses are partially restored by 9-cis-retinyl acetate administration in adulthood. Following treatment, two-photon calcium imaging revealed increases in the number and response amplitude of visually responsive neurons in the primary visual cortex (V1). In particular, retinoid treatment enhanced responses from the ipsilateral eye, restoring the normal balance of eye-specific responses in V1. Additionally, the treatment rescued the modulation of cortical responses by arousal. These findings illustrate the significant plasticity of the adult central visual system and underscore the therapeutic potential of retinoid administration for adults with retinal diseases.

Keywords: 9-cis-retinyl acetate; Leber congenital amaurosis; Lrat; V1; binocularity; childhood blindness; retinal degeneration; retinal disease; retinoid treatment; two-photon calcium imaging.

MeSH terms

Animals
Calcium
Eye Proteins
Mice
Retina
Retinal Degeneration* / drug therapy
Retinoids / pharmacology
Retinoids / therapeutic use
cis-trans-Isomerases

Substances

Retinoids
cis-trans-Isomerases
Calcium
Eye Proteins

Abstract

MeSH terms

Substances

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