title: Effect of visible light on normal and P23H-3 transgenic rat retinas: characterization of a novel retinoic acid derivative present in the P23H-3 retina.
abstract: Transgenic rats with the P23H mutation in rhodopsin exhibit increased susceptibility to light damage, compared with normal animals. It is known that light-induced retinal damage requires repetitive bleaching of rhodopsin and that photoreceptor cell loss is by apoptosis; however, the underlying molecular mechanism(s) leading to photoreceptor cell death are still unknown. Photoproducts, such as all-trans retinal or other retinoid metabolites, released by the extensive bleaching of rhodopsin could lead to activation of degenerative processes, especially in animals genetically predisposed to retinal degenerations. Using wild-type and transgenic rats carrying the P23H opsin mutation, we evaluated the effects of acute intense visible light on retinoid content, type and distribution in ocular tissues. Rats were exposed to green light (480-590 nm) for 0, 5, 10, 30 and 120 min. Following light treatment, rats were sacrificed and neural retinas were dissected free of the retinal pigment epithelium. Retinoids were extracted from retinal tissues and then subjected to HPLC and mass spectral analysis. We found that the light exposure affected relative levels of retinoids in the neural retina and retinal pigment epithelium of wild-type and P23H rat eyes similarly. In the P23H rat retina but not the wild-type rat retina, we found a retinoic acid-like compound with an absorbance maximum of 357 nm and a mass of 304 daltons. Production of this retinoic acid-like compound in transgenic rats is influenced by the age of the animals and the duration of light exposure. It is possible that this unique retinoid may be involved in the process of light-induced retinal degeneration.
authors.affiliation: Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Duncan
authors.forename: Barbara
authors.initials: B
authors.lastname: Wiggert
authors.forename: Noel
authors.initials: N
authors.lastname: Whittaker
authors.forename: Ruth
authors.initials: R
authors.lastname: Darrow
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Organisciak
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D008027:Light / Q000009:adverse effects*; D009154:Mutation; D051381:Rats; D012160:Retina / Q000528:radiation effects*; D012243:Rhodopsin / Q000235:genetics; D014212:Tretinoin / Q000302:isolation & purification / Q000528:radiation effects
chemical_list: D014212:Tretinoin; D012243:Rhodopsin