LiGluR restores visual responses in rodent models of inherited blindness

Natalia Caporale, Kathleen D. Kolstad, Trevor Lee, Ivan Tochitsky, Deniz Dalkara, Dirk Trauner, Richard Kramer, Yang Dan, Ehud Y. Isacoff, John G. Flannery

Research output: Contribution to journalArticle

Abstract

Inherited retinal degeneration results from many different mutations in either photoreceptor-specific or nonphotoreceptor-specific genes. However, nearly all mutations lead to a common blinding phenotype that initiates with rod cell death, followed by loss of cones. In most retinal degenerations, other retinal neuron cell types survive for long periods after blindness from photoreceptor loss. One strategy to restore light responsiveness to a retina rendered blind by photoreceptor degeneration is to express light-regulated ion channels or transporters in surviving retinal neurons. Recent experiments in rodents have restored light-sensitivity by expressing melanopsin or microbial opsins either broadly throughout the retina or selectively in the inner segments of surviving cones or in bipolar cells. Here, we present an approach whereby a genetically and chemically engineered light-gated ionotropic glutamate receptor (LiGluR) is expressed selectively in retinal ganglion cells (RGCs), the longest-surviving cells in retinal blinding diseases. When expressed in the RGCs of a well-established model of retinal degeneration, the rd1 mouse, LiGluR restores light sensitivity to the RGCs, reinstates light responsiveness to the primary visual cortex, and restores both the pupillary reflex and a natural light-avoidance behavior.

Original languageEnglish (US)
Pages (from-to)1212-1219
Number of pages8
JournalMolecular Therapy
Volume19
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Ionotropic Glutamate Receptors
Blindness
Rodentia
Light
Retinal Degeneration
Retinal Ganglion Cells
Retinal Neurons
Photophobia
Retina
Retinal Photoreceptor Cell Inner Segment
Pupillary Reflex
Avoidance Learning
Opsins
Retinal Diseases
Mutation
Visual Cortex
Ion Channels
Cell Death
Phenotype
Genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Caporale, N., Kolstad, K. D., Lee, T., Tochitsky, I., Dalkara, D., Trauner, D., ... Flannery, J. G. (2011). LiGluR restores visual responses in rodent models of inherited blindness. Molecular Therapy, 19(7), 1212-1219. https://doi.org/10.1038/mt.2011.103

LiGluR restores visual responses in rodent models of inherited blindness. / Caporale, Natalia; Kolstad, Kathleen D.; Lee, Trevor; Tochitsky, Ivan; Dalkara, Deniz; Trauner, Dirk; Kramer, Richard; Dan, Yang; Isacoff, Ehud Y.; Flannery, John G.

In: Molecular Therapy, Vol. 19, No. 7, 07.2011, p. 1212-1219.

Research output: Contribution to journalArticle

Caporale, N, Kolstad, KD, Lee, T, Tochitsky, I, Dalkara, D, Trauner, D, Kramer, R, Dan, Y, Isacoff, EY & Flannery, JG 2011, 'LiGluR restores visual responses in rodent models of inherited blindness', Molecular Therapy, vol. 19, no. 7, pp. 1212-1219. https://doi.org/10.1038/mt.2011.103
Caporale N, Kolstad KD, Lee T, Tochitsky I, Dalkara D, Trauner D et al. LiGluR restores visual responses in rodent models of inherited blindness. Molecular Therapy. 2011 Jul;19(7):1212-1219. https://doi.org/10.1038/mt.2011.103
Caporale, Natalia ; Kolstad, Kathleen D. ; Lee, Trevor ; Tochitsky, Ivan ; Dalkara, Deniz ; Trauner, Dirk ; Kramer, Richard ; Dan, Yang ; Isacoff, Ehud Y. ; Flannery, John G. / LiGluR restores visual responses in rodent models of inherited blindness. In: Molecular Therapy. 2011 ; Vol. 19, No. 7. pp. 1212-1219.
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