Duncan Todd, Wiggert Barbara, Whittaker Noel, Darrow Ruth, Organisciak Daniel T
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Photochem Photobiol. 2006 May-Jun;82(3):741-5. doi: 10.1562/2005-10-05-RA-712.
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.
与正常动物相比，视紫红质中存在P23H突变的转基因大鼠对光损伤的易感性增加。已知光诱导的视网膜损伤需要视紫红质的反复漂白，并且光感受器细胞的丢失是通过凋亡实现的；然而，导致光感受器细胞死亡的潜在分子机制仍然未知。视紫红质广泛漂白释放的光产物，如全反式视黄醛或其他类视黄醇代谢产物，可能导致退行性过程的激活，特别是在具有视网膜变性遗传易感性的动物中。我们使用携带P23H视蛋白突变的野生型和转基因大鼠，评估了急性强光对眼组织中类视黄醇含量、类型和分布的影响。将大鼠暴露于绿光（480 - 590 nm）下0、5、10、30和120分钟。光照处理后，处死大鼠并将神经视网膜从视网膜色素上皮中分离出来。从视网膜组织中提取类视黄醇，然后进行高效液相色谱和质谱分析。我们发现光照对野生型和P23H大鼠眼睛的神经视网膜和视网膜色素上皮中类视黄醇的相对水平有类似的影响。在P23H大鼠视网膜而非野生型大鼠视网膜中，我们发现了一种类视黄酸样化合物，其最大吸收波长为357 nm，分子量为304道尔顿。转基因大鼠中这种类视黄酸样化合物的产生受动物年龄和光照持续时间的影响。这种独特的类视黄醇可能参与了光诱导的视网膜变性过程。
