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

doi:10.1073/pnas.150236297

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

Journal article

Open access

Peer reviewed

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 and Krzysztof Palczewski

Proceedings of the National Academy of Sciences - PNAS, Vol.97(15), pp.8623-8628

07/18/2000

DOI: 10.1073/pnas.150236297

PMCID: PMC26998

PMID: 10869443

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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.

Retinaldehyde - therapeutic use

Retinoids - metabolism

Blindness - physiopathology

Humans

Pigment Epithelium of Eye - physiopathology

Retinaldehyde - administration & dosage

Male

Retinaldehyde - metabolism

Retinal Degeneration - metabolism

Retinoids - administration & dosage

Retinoids - therapeutic use

Time Factors

Female

Blindness - drug therapy

Child

cis-trans-Isomerases

Carrier Proteins

Disease Models, Animal

Proteins - physiology

Administration, Oral

Retinal Degeneration - drug therapy

Retinal Degeneration - physiopathology

Mice, Knockout

Proteins - genetics

Animals

Mice

Eye Proteins

Retinal Rod Photoreceptor Cells - physiopathology

Details

Title: Subtitle: Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness
Creators: J Preston Van Hooser - Departments of Ophthalmology, Chemistry, and Pharmacology, University of Washington, Seattle, WA 98195, USA
Tomas S Aleman
Yu-Guang He - University of Washington
Artur V Cideciyan
Vladimir Kuksa
Steven J Pittler
Edwin M Stone
Samuel G Jacobson
Krzysztof Palczewski
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.97(15), pp.8623-8628
DOI: 10.1073/pnas.150236297
PMID: 10869443
PMCID: PMC26998
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: United States
Grant note: R01 EY009339 / NEI NIH HHS F32 EY007031 / NEI NIH HHS T32 EY007031 / NEI NIH HHS EY07031 / NEI NIH HHS EY05627 / NEI NIH HHS EY09339 / NEI NIH HHS
Language: English
Date published: 07/18/2000
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979938302771

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