Vitamin A and Vision.
Visual systems detect light by monitoring the effect of photoisomerization of a chromophore on the release of a neurotransmitter from sensory neurons, known as rod and cone photoreceptor cells in vertebrate retina. In all known visual systems, the chromophore is 11-cis-retinal complexed with a protein, called opsin, and photoisomerization produces all-trans-retinal. In mammals, regeneration of 11-cis-retinal following photoisomerization occurs by a thermally driven isomerization reaction. Additional reactions are required during regeneration to protect cells from the toxicity of aldehyde forms of vitamin A that are essential to the visual process. Photochemical and phototransduction reactions in rods and cones are identical; however, reactions of the rod and cone visual pigment regeneration cycles differ, and perplexingly, rod and cone regeneration cycles appear to use different mechanisms to overcome the energy barrier involved in converting all-trans- to 11-cis-retinoid. Abnormal processing of all-trans-retinal in the rod regeneration cycle leads to retinal degeneration, suggesting that excessive amounts of the retinoid itself or its derivatives are toxic. This line of reasoning led to the development of various approaches to modifying the activity of the rod visual cycle as a possible therapeutic approach to delay or prevent retinal degeneration in inherited retinal diseases and perhaps in the dry form of macular degeneration (geographic atrophy). In spite of great progress in understanding the functioning of rod and cone regeneration cycles at a molecular level, resolution of a number of remaining puzzling issues will offer insight into the amelioration of several blinding retinal diseases.
Departments of Ophthalmology and Biochemistry, School of Medicine, University of Washington, 98195, Seattle, WA, USA. jsaari@u.washington.edu.|Department of Biochemistry, University of Washington, 357350, 98195, Seattle, WA, USA. jsaari@u.washington.edu.
John C
JC
Saari
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003624:Darkness; D005544:Forecasting; D057092:Geographic Atrophy / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D008027:Light; D015394:Molecular Structure; D010777:Photochemistry; D017785:Photons; D000069583:Pregabalin / Q000494:pharmacology / Q000627:therapeutic use; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology* / Q000528:radiation effects; D055213:Retinal Pigment Epithelium / Q000502:physiology; D012168:Retinal Pigments / Q000502:physiology* / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology* / Q000528:radiation effects; D012172:Retinaldehyde / Q000378:metabolism; D012545:Schiff Bases; D014714:Vertebrates / Q000502:physiology; D014785:Vision, Ocular / Q000502:physiology*; D014801:Vitamin A / Q000502:physiology* / Q000528:radiation effects; D019745:cis-trans-Isomerases / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D000069583:Pregabalin; D012168:Retinal Pigments; D012172:Retinaldehyde; D012545:Schiff Bases; D014801:Vitamin A; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C020932:11-cis-retinal-binding protein
11-cis retinal; 11-cis-retinol; All-trans-retinal; All-trans-retinol; CRALBP; Cone; RPE65; Regeneration; Retina; Rod; Vision; Visual cycle