title: A History of the Classical Visual Cycle.
abstract: The visual cycle, the biochemical process by which the light-sensitive isomer of vitamin A is continually recycled, is crucial to vision in a healthy eye. More than 150 years of research into this remarkable biochemical process has given invaluable understanding in debilitating visual diseases that impact thousands of individuals worldwide, many of them children. The visual cycle spans photoreceptor cells in the retina and the underlying retinal pigment epithelium (RPE) and requires a protein called RPE65 for its function. In many ways, RPE65 is the capstone to the cyclical processing of vitamin A in the eye, and the discovery of this retinol isomerase helped fill a critical gap in the understanding of retinoid processing in vision. This chapter will focus on the history of visual cycle research, from the first experiments well over a century ago to the discovery of RPE65. Because of the undeniable importance of RPE65 in the visual cycle, this chapter will also focus on the protein structure and mechanism by which it converts light-insensitive all-trans-vitamin A to light-sensitive 11-cis-vitamin A for continued visual function. Finally, this chapter will briefly discuss RPE65 and its known disease associations in the clinical setting. Thanks to the efforts of researchers for well over a century in studying the visual cycle, the medical community is now poised to make significant gains in the treatment of blindness.
authors: Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, USA. Electronic address: wright.charles@uky.edu.
authors: Charles B
authors: CB
authors: Wright
authors: Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, Maryland, USA.
authors: T Michael
authors: TM
authors: Redmond
authors: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors: John M
authors: JM
authors: Nickerson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D012164:Retinal Diseases / Q000235:genetics / Q000473:pathology; D014795:Visual Pathways / Q000378:metabolism*; D019745:cis-trans-Isomerases / Q000737:chemistry / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
chemical_list: D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
keywords: RPE65; Visual cycle; Vitamin A