NORMAL CATARACT MODEL--DEFINITION AND MECHANISMS

描述：一个正常的长寿，黑眼睛的小鼠品系， 研究了（C57 BL/6xDBA/2）F1杂交小鼠的晚年发病率 白内障 这种发生率在很晚的生命中接近100%， 初步研究表明，在老年期间， 对小鼠 白内障发生的时间及其与 其它眼睛或全身性病理学将这种小鼠模型 其他人现在使用。 这些细节表明， 是一种较理想的人类衰老性白内障模型。 的意图是 申请人完成涉及发生时间的模型研究， 涉及的遗传背景、透镜的组织病理学， 邻接的眼睛，以及氧化DNA损伤在 其因果关系。 将确定这种小鼠品系是否是 其独特之处在于其非常高的白内障晚期发病率或其他 菌株将提供类似的结果。 特别重要的是 事实上，终身热量限制（CR）为随意（AL）的60% 饮食可显著降低发病率，并延缓 白内障 CR已被证明可以减少对细胞的氧化损伤 和它们的DNA，并保持细胞的复制能力， 体内和体外。 存在的DNA损伤量，测量为 或单链或双链DNA断裂，以及端粒 缩短，将确定在透镜上皮细胞的 按时间顺序间隔的小鼠组。 这将在两个 未处理的透镜细胞和接受体外培养的晶状体细胞中， 氧化挑战 任何影响的终身光暴露将是 有记录 所有这些测量结果都将与 的透镜细胞在培养中形成大的克隆， 一种可靠的生理细胞老化测量方法。 本研究将 定义人类年龄相关性白内障形成的小鼠模型， 用它来提供有关氧化损伤的有害作用的信息 与透镜上皮细胞DNA的结合，这与白内障的发展有关。

DESCRIPTION: A normal long-lived, dark-eyes mouse strain, the (C57BL/6xDBA/2) F1 hybrid mouse has been studied for late life incidence of cataracts. This incidence approaches 100% in very late life and, in preliminary studies, appears to accumulate progressively during old age in mice. The time of cataract occurrence and its non-association with other eye or general systemic pathologies differentiate this mouse model from others now in use. These particulars indicate that it promises to be an ideal model for the human aging cataract. It is the intent of the applicants to complete the model studies involving time of occurrence, the genetic background involved, the histopathology of the lens and adjoining eyes, and the possible importance of oxidative DNA damage in its causation. It will be determined whether this mouse strain is unique in its very high late incidence of cataracts or whether other strains will provide similar findings. Of particular importance is the fact that life long caloric restriction (CR) at 60% of ad libitum (AL) diet significantly reduces the incidence and delays the appearance of the cataracts. CR has been shown to reduce oxidative damage to cells and their DNA and to preserve the replicative capacity of cells both in vivo and in vitro. The amount of DNA damage present, measured as either or single or double stranded DNA breaks, as well as telomeric shortening, will be determined in the lens epithelial cells of chronologically spaced groups of mice. This will be done both in untreated lens cells and in those that have received an in vitro oxidative challenge. Any effects of lifetime light exposure will be accounted for. All of these measurements will be matched to the ability of the lens cells from the same donors to form large clones in culture, a reliable measurement of physiological cellular aging. This study will define a mouse model for human age-related cataract formation and will use it to provide information on the harmful role of oxidative damage to lens epithelial cell DNA, correlating this with cataract development.