CLINICAL EPIDEMIOLOGY OF RETINAL DEGENERATIONS

描述：（申请人摘要）类胡萝卜素缺乏症与 年龄相关性黄斑变性（AMD）和大量证据 降低类胡萝卜素对炎症过程的生物利用度。K23 该项目测试了系统性慢性低级别 炎症可能通过以下方式在某些AMD中起作用：（1）直接炎症， 炎症/氧化损伤布鲁赫膜-视网膜色素 上皮-感光复合体，或（2）通过降低生物利用度 黄斑类胡萝卜素、叶黄素和玉米黄质进入视网膜， 系统池的消耗，或通过视网膜内池的消耗。 候选人将参加一系列指导临床研究 同时进行以下一系列研究， 是为了开始检验这个假设而设计的。(1)分析现有的 第三次全国健康和营养检查调查（NHANES-III）数据集， 评估血清C反应蛋白水平与 关于AMD (2)老年人AMD的现况调查 已经参与了正在进行的健康，衰老和身体动态 组成（健康ABC）研究。详细的视网膜检查将在 200名可能患有某种程度AMD的受试者和100名未受影响的个体。 将估计叶黄素和玉米黄质的视网膜内光密度 在每名受试者中，通过基于 异色闪烁光度法原理黄斑外观将是 以国际认可的系统记录并分级。 在此期间收集的血液样本，作为健康ABC研究的一部分 将分析方案的炎症标志物水平， 类胡萝卜素这些措施之间的相关性和相关差异 将确定是否存在AMD，以测试基本的 炎症-类胡萝卜素-AMD假说的原则。未来的R 01提案将 无论实际机制是直接的还是间接的。 职业发展活动包括：正式的流行病学研究， 生物统计学;导师指导的复杂数据分析培训， 现有研究的数据集以及临床研究设计和实施中的数据集 流行病学研究;黄斑色素光密度测量培训 方法;以及黄斑照片分析方法和眼底的培训 摄影阅读中心业务。

DESCRIPTION: (Applicant's Abstract) Carotenoid deficiency has been implicated in age-related macular degeneration (AMD) and substantial evidence links reduced bioavailability of carotenoids to inflammatory processes. This K23 project tests the unique hypothesis that systemic chronic low-grade inflammation may play a role in some AMD by means of either (1) a direct inflammatory/oxidative insult to the Bruch's membrane-retinal pigment epithelium- photoreceptor complex, or (2) by reducing the bioavailability of the macular carotenoids, lutein and zeaxanthin to the retina, either via depletion of the systemic pool, or via depletion of the intraretinal pool. The candidate will partake in a series of mentored clinical-research development activities while conducting the following sequence of studies that are designed to begin testing this hypothesis. (1) An analysis on the existing Third National Health and Nutrition Examination Survey (NHANES-III) data set to evaluate the possible association between serum levels of C-reactive protein and AMD. (2) A cross-sectional investigation on AMD in an elderly population already participating in the ongoing Dynamics of Health, Aging, and Body Composition (Health ABC) Study. A detailed retinal exam will be performed on 200 subjects likely to have some level of AMD and 100 non-affected individuals. The intraretinal optical density of lutein and zeaxanthin will be estimated non-invasively in each subject by means of a validated method based on the principle of heterochromatic flicker photometry. Macular appearance will be documented photographically and graded with an internationally approved system. Blood samples collected during this period, as part of the Health ABC Study protocol will be analyzed for levels of markers of inflammation and carotenoids. Correlations between these measures and differences associated with presence or absence of AMD will be determined in order to test the basic tenet of the inflammation-carotenoid-AMD hypothesis. Future R01 proposals would pursue whether the actual mechanisms are direct or indirect. Career development activities include: formal studies of epidemiology and biostatistics; guided training by the mentor in complex data analyses using data sets from existing studies and in design and implementation of clinical epidemiologic studies; training in macular pigment optical density measurement methods; and training in macular photograph analysis methods and fundus photography Reading Center operations.