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BN Wiggert, T Duncan, RK Kutty, RM Darrow, DT Organisciak; The Role of Retinoids, Genetics, and Age in Retinal Light Damage . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4575.
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Purpose: Photoactivation of rhodopsin results in the formation of all-trans retinal, which in turn is converted to all-trans retinol through enzymatic reduction. Some of the retinaldehyde generated by rhodopsin bleaching could also be oxidized to retinoic acid, a retinoid known to regulate many genes at the transcriptional level. In light exposed transgenic rats carrying the P23H mutation in the opsin gene we identified a retinoic acid-like compound present in both retina and RPE/eyecups. It is possible that light-mediated production of retinoic acid and/or retinoic acid-like compounds could result in the activation of degenerative processes, particularly in aged animals or in animals genetically predisposed to retinal degenerations. The purpose of this study was to evaluate the effect of acute, intense, visible light on the production of retinoic acid and retinoic acid-like compounds in the eyes of normal and transgenic rats carrying the P23H mutation in the opsin gene. Methods: Rats were maintained under dim cyclic light conditions until they were either 4 or 9 weeks of age. Rats were dark adapted and exposed to bright white or green light (490-580 nm) for 0, 10, or 30 minutes. Following treatment, rats were killed immediately in a CO2 chamber, neural retinas were dissected free of the retinal pigment epithelium, and retinoids extracted and then analyzed by HPLC. Selected peaks were also analyzed by electrospray ionization mass spectrometry. Results: A compound has been identified in light exposed P23H retina and RPE/eyecup that has an absorbance maximum of 357 nm, which is similar to retinoic acid. In samples taken from 9 week old P23H rats this compound had a molecular mass of 304. We did not observe this compound in the light exposed normal rat retina or RPE/eyecup. Production of this retinoic acid-like compound is influenced by the age of the animals and the duration of light exposure. For example, in retinas and RPE/eyecups of P23H rats at 4 weeks of age, the type of light as well as the duration of light exposure had no effect on the production of this compound. However, in the RPE/eyecups of P23H rats at 9 weeks of age, 30 minutes of light exposure resulted in a 4-fold increase in the amount of this compound. Conclusion: These results support the idea that a retinoid metabolite(s) may be an important factor in the retinal damage generated by exposure to intense visible light in P23H rats.
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