LIGHT TOXICITY AND RETINAL DEGENERATION AND AGING

来自流行病学和实验室研究的令人信服的证据表明 光毒性在与年龄相关的疾病的发展中起作用 视网膜的病理学；然而，一个重要的悬而未决的问题是 视网膜损伤对曝光波长的依赖性。总目标 所提出的研究是为了检验不同光谱的假设 光伤害的等级是存在的，它们可以通过 分开的效果和机制。使用白化病和白化病的方法 有色素的老鼠被暴露在精确定义的波长的光中， 光子剂量和场均匀度，以及多学科方法 评估他们视网膜的光诱导变化，具体目标是 这项研究的目的是识别光损伤的光谱类别 1)动作谱测定和形态观察的基础；2) 视紫红质水平和再生动力学的变化； 视蛋白合成的下调；4)细胞凋亡在 光感受器与视网膜色素上皮细胞死亡； 氧化机制的参与和对β-半胱氨酸的保护作用 胡萝卜素。 拟议的研究将提供有关 视网膜光毒性的影响及其机制可能有助于 阐明它在视网膜老化中的作用。此外，这些信息应该是 有助于设计旨在防止光诱导的建议 视网膜病理通过过滤特定波长的光，并通过 对光诱导的氧化提供足够的保护。这些 考虑到最近的流行病学情况，采取措施可能是至关重要的 有证据表明，累积的阳光暴露量与 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).