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PMID: 16968212 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Diseases caused by defects in the visual cycle: retinoids as potential therapeutic agents.

Annual review of pharmacology and toxicology ·Vol. 47 ·2007-00-00 ·Pages 469-512

Travis GH, Golczak M, Moise AR, Palczewski K

Abstract

Absorption of a photon by an opsin pigment causes isomerization of the chromophore from 11-cis-retinaldehyde to all-trans-retinaldehyde. Regeneration of visual chromophore following light exposure is dependent on an enzyme pathway called the retinoid or visual cycle. Our understanding of this pathway has been greatly facilitated by the identification of disease-causing mutations in the genes coding for visual cycle enzymes. Defects in nearly every step of this pathway are responsible for human-inherited retinal dystrophies. These retinal dystrophies can be divided into two etiologic groups. One involves the impaired synthesis of visual chromophore. The second involves accumulation of cytotoxic products derived from all-trans-retinaldehyde. Gene therapy has been successfully used in animal models of these diseases to rescue the function of enzymes involved in chromophore regeneration, restoring vision. Dystrophies resulting from impaired chromophore synthesis can also be treated by supplementation with a chromophore analog. Dystrophies resulting from the accumulation of toxic pigments can be treated pharmacologically by inhibiting the visual cycle, or limiting the supply of vitamin A to the eyes. Recent progress in both areas provides hope that multiple inherited retinal diseases will soon be treated by pharmaceutical intervention.

MeSH Terms
Animals Genetic Therapy Humans Models, Animal Photoreceptor Cells/drug effects Retina/physiopathology Retinal Diseases/drug therapy,physiopathology Retinoids/pharmacology,therapeutic use Vision Disorders/drug therapy,physiopathology Vitamin A/adverse effects,therapeutic use Vitamins/adverse effects,therapeutic use
Chemicals
Retinoids Vitamins Vitamin A
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Travis Gabriel H
Department of Ophthalmology, UCLA School of Medicine, Los Angeles, CA 90095, USA. travis@jsei.ucla.edu
Golczak Marcin
Moise Alexander R
Palczewski Krzysztof
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Article Info
Journal
Annual review of pharmacology and toxicology
Abbr.
Annu Rev Pharmacol Toxicol
ISSN
0362-1642
DOI
10.1146/annurev.pharmtox.47.120505.105225
Email
travis@jsei.ucla.edu
Published
2007-00-00
Pages
469-512
Language
English
Region
United States
NLM ID
7607088
PMCID
PMC2442882
Subset
IM
Grants
NEI NIH HHS · R01 EY009339 · United States
NEI NIH HHS · P30 EY011373 · United States
NEI NIH HHS · R01 EY011713-15 · United States
NEI NIH HHS · R01 EY011713 · United States
NEI NIH HHS · EY 11373 · United States
NEI NIH HHS · R01 EY011713-16 · United States
NEI NIH HHS · R01 EY011713-14 · United States
NEI NIH HHS · P30 EY011373-119005 · United States
NEI NIH HHS · EY 09339 · United States
NEI NIH HHS · EY 11713 · United States
NEI NIH HHS · EY 015844 · United States
NEI NIH HHS · R01 EY015844 · United States
NEI NIH HHS · R01 EY009339-18 · United States
External Links
PubMed source DOI: 10.1146/annurev.pharmtox.47.120505.105225 PMC Full Text View journal details
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