Genetic defects in vitamin A metabolism of the retinal pigment epithelium
- PMID: 12876835
- DOI: 10.1159/000072044
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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