NORMAL CATARACT MODEL--DEFINITION AND MECHANISMS

描述：一种正常的长寿、黑眼睛的小鼠品系 (C57BL/6xDBA/2)F1杂交小鼠晚年发病率的研究 白内障的症状。这种发病率在晚年接近100%，在 初步研究，似乎是在老年时逐渐积累的 在老鼠身上。白内障的发生时间及其与白内障的非关联性 其他眼部或全身病理改变可区分此小鼠模型 从目前正在使用的其他设备中分离出来。这些细节表明，它承诺 是研究人类老年性白内障的理想模型。它的目的是为了 申请者完成涉及发生时间的模型研究， 所涉及的遗传背景，晶状体的组织病理学和 以及氧化DNA损伤在眼球疾病中的可能重要性 它的因果关系。将确定这种老鼠品系是否是 其独特之处在于白内障的晚期发病率很高，或者其他 菌株将提供类似的发现。特别重要的是 终身热量限制(CR)为60%的随意热量限制(AL) 饮食显著降低了发病率，并延迟了 白内障。铬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，以 或单链或双链DNA断裂，以及端粒 缩短，将在晶状体上皮细胞中确定 按时间间隔排列的老鼠群。这将在两个版本中完成 未经处理的晶状体细胞和那些接受了体外培养的晶状体细胞 氧化挑战。终生光照的任何影响都将是 算进去了。所有这些测量都将与能力匹配 来自相同捐赠者的晶状体细胞在培养中形成大克隆， 一种可靠的生理细胞老化测量方法。这项研究将 为人类老年性白内障的形成和意志定义一个小鼠模型 使用它来提供有关氧化损伤的有害作用的信息 晶状体上皮细胞DNA，这与白内障的发生有关。

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.