Genetic defects in vitamin A metabolism of the retinal pigment epithelium
Abstract
The metabolism of vitamin A and cycling of retinoids between the retinal pigment epithelium (RPE) and the neural retina is a complex process involving a specialized enzymes and proteins. Mutations in a number of the corresponding genes are responsible for various forms of inherited retinal dystrophy and dysfunction. Research into the causes and treatment of retinal diseases resulting from defects in vitamin A metabolism is currently the subject of intense interest, since disorders affecting RPE function are, in principle, more accessible to therapeutic intervention than those affecting the proteins of the photoreceptor cells. In this chapter we present an overview of the visual cycle, as well as the function of the known RPE genes involved in the conversion of vitamin A (all-trans retinol) to 11-cis retinal, the chromophore of the visual pigments. We describe the identification of disease-associated mutations in this set of genes in patients with diverse forms of retinal dystrophy and dysfunction, as well as the spectrum of mutations and associated phenotypes. We also discuss the results of recent studies using animal models of the disease caused by mutations of RPE65. On the basis of these advances, it is hoped that patients with defects in RPE vitamin A metabolism will be among the first successfully treated by targeted therapies likely to become available in the near future.
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Defects in the RPE contribute to diseases such as macular degeneration and retinitis pigmentosa, which result in vision problems.
“Defects in the RPE contribute to diseases such as macular degeneration and retinitis pigmentosa, which result in vision problems [34], [35].”
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The Retinal Pigment Epithelium in Visual Function
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- Authors
- Thompson, D. A., & Gal, A.
- Affiliations
- University of Michigan (US)
- ORCID
- Thompson, D.A.
- Venue
- Developments in Ophthalmology
- Publisher
- KARGER
- Published
- 2003
- Volume
- 37
- Pages
- 141-154
- OpenAlex
- W1493132866
- Cited by
- 47
- References
- 7
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 5 · 2012: 3
- FWCI
- 6.57
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- KARGER eBooks (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- retinal pigment epithelium, vitamin A metabolism, visual cycle, RPE65, inherited retinal disease, disease-associated mutations, 11-cis-retinal, all-trans-retinol, targeted therapy
- MeSH terms
- Humans, Metabolism, Inborn Errors, Pigment Epithelium of Eye, Vitamin A
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