CLINICAL EPIDEMIOLOGY OF RETINAL DEGENERATIONS

视网膜变性的临床流行病学

• 批准号: 6331691
• 负责人: ALESSANDRO IANNACCONE
• 金额: $ 14.62万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6331691
• 关键词: acute phase protein; carotenoids; clinical research; disease /disorder etiology; epidemiology; eye fundus photography; high performance liquid chromatography; human old age (65+); human subject; macular degeneration; noninvasive diagnosis; nutrient bioavailability; retina degeneration; retinal pigment epithelium; vision tests; visual photoreceptor; vitamin deficiency

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.

描述：（申请人的摘要）类胡萝卜素缺乏症已牵涉 与年龄相关的黄斑变性（AMD）和大量证据联系 类胡萝卜素对炎症过程的生物利用度降低。这个K23 项目测试全身慢性低级的独特假设 炎症可能通过（1）直接在某些AMD中发挥作用 对BRUCH的膜 - 视网膜色素的炎症/氧化侮辱 上皮光感受器复合物，或（2）通过降低生物利用度 黄斑类胡萝卜素，叶黄素和Zeaxanthin到视网膜，要么通过 全身池的耗竭，或通过视网膜内池的耗竭。 候选人将参加一系列指导的临床研究 开发活动同时进行以下研究顺序 旨在开始检验这一假设。 （1）对现有的分析 第三个国家卫生和营养检查调查（NHANES-III）数据集 评估C反应蛋白血清水平之间可能的关联 和AMD。 （2）对老年人口中AMD的横断面调查 已经参与健康，衰老和身体的动态 组成（健康ABC）研究。将对视网膜检查进行详细的检查 200名受试者可能具有一定程度的AMD和100个未受影响的人。 将估计叶黄素和玉米黄质的视网膜内光密度 通过基于经过验证的方法在每个主题中无创 异质闪烁光度法的原理。黄斑外观将是 在摄影上记录并通过国际批准的系统进行分级。 作为健康ABC研究的一部分，在此期间收集的血液样本 协议将分析炎症标记水平和 类胡萝卜素。这些措施与相关差异之间的相关性 在存在或不存在AMD的情况下，将确定测试基本 炎症 - 羟基苯酚-AMD假设的原则。未来的R01建议将 追求实际机制是直接的还是间接的。 职业发展活动包括：流行病学和 生物统计学；导师在复杂数据分析中使用指导培训 来自现有研究以及临床设计和实施的数据集 流行病学研究；黄斑色素的培训光密度测量 方法;以及黄斑照片分析方法和眼底培训 摄影阅读中心操作。