Macular Pigment in Aging and Disease

 描述（由申请人提供）：本提案的目的是评估黄斑色素（MP）水平作为年龄相关性黄斑变性（AMD）发展的可改变风险标志物，以及随着年龄的增长更广泛的神经视网膜和视觉功能丧失。一些先前的证据表明，MP，包括膳食类胡萝卜素叶黄素，玉米黄质和内消旋玉米黄质，随着年龄的增长而下降，并且保存MP可能有助于降低患上眼部疾病和/或视力丧失的风险，这些疾病和视力丧失随着年龄的增长而变得更加常见。这在以前的大型纵向研究中尚未得到评价。MP光密度（MPOD）可以简单和非侵入性地测量。因此，MPOD评估可能是有用的筛选，以确定个人，在中年，谁是年龄相关的视力损失的风险较高。评估MPOD的设备已经适应于临床使用，但需要解决MPOD与AMD和视力丧失的纵向关系的证据，以提出关于其适当使用的建议。如果MPOD预测AMD和/或年龄或疾病相关的视力丧失，那么早期评估将允许针对个体测试各种预防措施以降低风险，包括那些会增加黄斑色素的措施。 通过对眼相关眼病研究（CAREDS）队列中的类胡萝卜素进行前瞻性随访研究，可以以低成本获得解决纵向数据中差距的证据。在2001-2004年期间，对1,791名女性进行了MPOD、眼底照片（用于评估AMD）和视力测量。在妇女健康倡议中，每年对这一队列进行随访，确保随访损失低，记录死亡率和新的慢性疾病（包括常见的与年龄有关的眼病），并提供广泛的营养、遗传、生活方式和健康数据。 十三年后将进行随访，以提供第二组眼底照片，以记录MPOD与AMD发病率和/或进展的关系。其次，还将研究基线时的MPOD与随访时的结构和功能老化指标的关系。结构测量包括使用谱域光学相干断层扫描（SD-OCT）跨几个层和区域的视网膜厚度的新测量。功能指标包括基线和随访之间的视力丧失，以及随访时获得的其他次要指标。第三，将获得随访时的MPOD水平的测量，以允许MPOD随年龄下降的第一个直接纵向估计，并提供一个机会来探索在基线和随访之间，初始MPOD较高的女性以及叶黄素和玉米黄质摄入量较高的女性中，平均年龄相关的下降是否较低。这项拟议的研究将构成黄斑色素与衰老，年龄相关性视力丧失和AMD关系的最大和最长的现存调查，从而推进了解类胡萝卜素在随着年龄的增长保持视力方面的作用所需的知识，并为临床指南提供信息。

 DESCRIPTION (provided by applicant): The purpose of this proposal is to evaluate macular pigment (MP) levels as a modifiable risk marker for the development of age-related macular degeneration (AMD), and more generalized loss of neural retina and vision function with age. Some previous evidence suggests that MP, comprised of the dietary carotenoids lutein, zeaxanthin and meso-zeaxanthin, declines with age, and that preserving MP might help reduce risk for developing eye diseases and/or vision loss which become more common as we age. This has not been previously evaluated in large longitudinal studies. MP optical density (MPOD) can be simply and non-invasively measured. Therefore, MPOD assessment might be useful in screening to identify individuals, in middle-age, who are at higher risk for age-related vision los. Devices to assess MPOD are already adapted for clinical use, but evidence addressing longitudinal relationships of MPOD to AMD and vision loss is needed to make recommendations about their appropriate use. If MPOD predicts AMD and/or age- or disease-related vision loss, then early assessment would permit the targeting of individuals for testing a variety of preventive measures to lower risk, including those which would increase macular pigment. Evidence to address the gap in longitudinal data can be obtained at low cost by conducting a prospective follow-up study in the Carotenoids in Age-Related Eye Disease Study (CAREDS) cohort. MPOD, fundus photographs to assess AMD, and visual acuity measures were previously obtained in 1,791 women in 2001-2004. Annual follow-up of this cohort, in the Women's Health Initiative, assures low loss to follow up, documents mortality and new chronic diseases (including common age-related eye diseases), and provides extensive nutritional, genetic, lifestyle, and health data. Follow-up visits thirteen years later will be conducted to provide a second set of fundus photographs to document the relationships of MPOD to AMD incidence and/or progression. Second, MPOD at baseline will also be studied in relation to measures of structural and functional aging at follow-up. Structural measures include new measures of the thickness of the retina, across several layers and regions, using spectral domain optical coherence tomography (SD-OCT). Functional measures include the loss of visual acuity between baseline and follow-up, and additional secondary measures obtained at follow-up. Third, measures of MPOD levels at follow-up will be obtained to permit the first direct longitudinal estimate of MPOD declines with age, and to provide an opportunity to explore whether average age-related declines are lower in women with higher initial MPOD, and in women with higher intakes of lutein and zeaxanthin, between baseline and follow-up. The proposed research will constitute the largest and longest extant investigation of relationships of macular pigment to aging, age-related vision loss, and AMD, thereby advancing knowledge needed to understand the role of carotenoids in preserving vision with age and informing clinical guidelines.