LIGHT TOXICITY AND RETINAL DEGENERATION AND AGING

流行病学和实验室研究的有力证据表明， 光毒性在与年龄相关的 视网膜的病理学;然而，一个重要的未解决的问题涉及 视网膜损伤对曝光波长的依赖性。 总目标 的拟议研究是测试的假设，不同的光谱 光损伤的类别存在，并且它们可以通过 不同的影响和机制。使用的方法，其中白化病和 将有色大鼠暴露于精确限定波长的光， 光子剂量和场均匀性，以及多学科方法， 评估光诱导的视网膜变化， 这项研究的目的是确定光损伤的光谱类别， 1）作用光谱测定和形态观察的依据; 2） 视紫红质水平和再生动力学的改变; 3） 视蛋白合成的下调; 4）细胞凋亡在 光感受器和视网膜色素上皮细胞死亡;以及5） 氧化机制的参与和β- 胡萝卜素 拟议的研究将提供有关以下方面的重要信息： 视网膜光毒性的影响和机制，这可能有助于 阐明其在视网膜老化中的作用。此外，这些信息应 有助于设计旨在防止光诱导的建议 视网膜病理学通过过滤掉特定波长的光， 提供足够的保护以防止光诱导的氧化。这些 考虑到最近的流行病， 有证据表明，累积的阳光照射与 患老年性黄斑变性（AMD）的风险增加。

Compelling evidence from epidemiological and laboratory studies suggests that light toxicity plays a role in the development of age-related pathology in the retina; however, an important unresolved issue concerns the dependence of retinal damage on exposure wavelength. The overall goal of the proposed research is to test the hypothesis that different spectral classes of light damage exist, and that they can be distinguished by separate effects and mechanisms. Using methodology by which albino and pigmented rats are exposed to light of precisely defined wavelength, photon dose, and field uniformity, and a multidisciplinary approach for assessing light-induced changes in their retinas, the specific objectives of this research are to identify spectral classes of light damage on the basis of 1) action spectra determination and morphologic observation; 2) alterations in rhodopsin levels and regeneration kinetics; 3) downregulation of opsin synthesis; 4) the role of apoptosis in photoreceptor and retinal pigment epithelial cell death; and 5) involvement of oxidative mechanisms and a protective role for beta- carotene. The proposed studies will provide important information regarding the effects and mechanisms of retinal phototoxicity which could help to clarify its role in retinal aging. Furthermore, this information should be useful for devising recommendations aimed at preventing light-induced retinal pathology by filtering out specific wavelengths of light, and by providing adequate protection against light-induced oxidation. These measures may he of paramount importance considering recent epidemiological evidence suggesting that cumulative sunlight exposure is associated with increased risk for acquiring age-related macular degeneration (AMD).