Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness

J. Preston Van Hooser, Tomas S. Aleman, Yu Guang He, Artur V. Cideciyan, Vladimir Kuksa, Steven J. Pittler, Edwin M. Stone, Samuel G. Jacobson, Krzysztof Palczewski

Research output: Contribution to journalArticle

202 Citations (Scopus)

Abstract

Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.

Original languageEnglish (US)
Pages (from-to)8623-8628
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number15
DOIs
StatePublished - Jul 18 2000

Fingerprint

Leber Congenital Amaurosis
Retinal Degeneration
Retinal Pigments
Retinoids
Blindness
Retinal Pigment Epithelium
Pharmacology
Mutation
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness. / Van Hooser, J. Preston; Aleman, Tomas S.; He, Yu Guang; Cideciyan, Artur V.; Kuksa, Vladimir; Pittler, Steven J.; Stone, Edwin M.; Jacobson, Samuel G.; Palczewski, Krzysztof.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 15, 18.07.2000, p. 8623-8628.

Research output: Contribution to journalArticle

Van Hooser, J. Preston ; Aleman, Tomas S. ; He, Yu Guang ; Cideciyan, Artur V. ; Kuksa, Vladimir ; Pittler, Steven J. ; Stone, Edwin M. ; Jacobson, Samuel G. ; Palczewski, Krzysztof. / Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 15. pp. 8623-8628.
@article{673f5809ef4944179541eafcbd497f08,
title = "Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness",
abstract = "Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.",
author = "{Van Hooser}, {J. Preston} and Aleman, {Tomas S.} and He, {Yu Guang} and Cideciyan, {Artur V.} and Vladimir Kuksa and Pittler, {Steven J.} and Stone, {Edwin M.} and Jacobson, {Samuel G.} and Krzysztof Palczewski",
year = "2000",
month = "7",
day = "18",
doi = "10.1073/pnas.150236297",
language = "English (US)",
volume = "97",
pages = "8623--8628",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "15",

}

TY - JOUR

T1 - Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness

AU - Van Hooser, J. Preston

AU - Aleman, Tomas S.

AU - He, Yu Guang

AU - Cideciyan, Artur V.

AU - Kuksa, Vladimir

AU - Pittler, Steven J.

AU - Stone, Edwin M.

AU - Jacobson, Samuel G.

AU - Palczewski, Krzysztof

PY - 2000/7/18

Y1 - 2000/7/18

N2 - Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.

AB - Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.

UR - http://www.scopus.com/inward/record.url?scp=0034682551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034682551&partnerID=8YFLogxK

U2 - 10.1073/pnas.150236297

DO - 10.1073/pnas.150236297

M3 - Article

VL - 97

SP - 8623

EP - 8628

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 15

ER -