The Role of Vitamin D in Retinal Diseases in Aging

描述（由申请人提供）：随着美国老龄化人口的增长，患有糖尿病性视网膜病变（DR）和年龄相关性黄斑变性（AMD）的视力威胁疾病的老年个体的数量预计在未来几十年内将增加.识别预防或延迟视力威胁疾病的新的可改变因素是重要的，因为它将减少用于治疗此类慢性疾病的卫生保健费用负担，并延长老年人可以独立并参与诸如驾驶、阅读、锻炼和食物准备等视力依赖性活动的年龄。维生素D缺乏和不足在大部分美国老龄化人口中普遍存在，并且维生素D已被证明除了潜在地调节血压和葡萄糖控制之外还具有抗炎和抗血管生成特性。拟议研究的长期目标是更好地了解维生素D状态在老年人中高度流行的视网膜疾病中的作用。很少有研究调查维生素D状态和DR之间的关系;尽管强有力的生物学原理支持维生素D状态是DR发展和进展的潜在可改变的风险因素。与此同时，两项大型流行病学研究的研究表明，维生素D缺乏或不足（25-羟基维生素D（25（OH）D）<50 nmol/L）的人更容易患AMD，但尚未进行AMD发病率和维生素D状况的前瞻性研究。我们假设，与维生素D充足的个体相比，维生素D缺乏或不足的个体更有可能患有AMD和DR，并且更有可能发展为AMD。本提案的目的是使用来自老年（45-64岁）社区动脉粥样硬化风险（ARIC）人群、双胞胎（非裔美国人和高加索人）队列的数据，研究维生素D状态与DR和AMD之间的关联。我们建议使用先前收集的数据，包括DR和AMD状态的分级视网膜照片，以及从1987-1995年收集的ARIC研究参与者的血清25（OH）D浓度测定，以及目前在随访研究（2011-2013）中获得的分级视网膜照片。具体而言，我们建议调查在第2次访视（1990-1992）时评估的维生素D状态与1）在第3次访视（1993-1995）时评估的1，657名糖尿病患者中存在DR和2）在第3次访视（1993-1995）时评估的11，532名参与者中存在AMD之间的相关性。第三，我们还首次提出在约2，346名ARIC参与者的样本中调查1990-1992年评估的维生素D状态与AMD发病率或进展（1993-1995年至2011-2013年）之间的关联。这项研究将促进我们对维生素D状态与老年人常见视力威胁性眼病的了解，并可能导致预防或减少这些疾病进展的新疗法。

DESCRIPTION (provided by applicant): The number of aging individuals with the vision threatening diseases of diabetic retinopathy (DR) and age- related macular degeneration (AMD) is projected to increase in the coming decades as the aging population of the United States grows. Identifying new modifiable factors that prevent or delay vision threatening disease is significant because it will reduce the burden of health care costs for treatment of such chronic diseases and extend the years that the elderly can be independent and participate in such vision dependent activities as driving, reading, exercise, and food preparation. Vitamin D deficiency and inadequacy is prevalent in a large portion of the aging US population, and vitamin D has been shown to have anti-inflammatory and anti- angiogenic properties, in addition to potentially modulating blood pressure and glucose control. The long-term goal of the proposed research is to better understand the role of vitamin D status in retinal diseases highly prevalent in aging individuals. Minimal research has investigated the association between vitamin D status and DR; although a strong biologic rationale supports vitamin D status as a potential modifiable risk factor for DR development and progression. At the same time, research in two large epidemiologic studies show that people with vitamin D deficiency or inadequacy (25-hydroxyvitamin D (25(OH)D)<50 nmol/L) are more likely to have prevalent AMD, but no prospective studies of AMD incidence and vitamin D status have been conducted. We hypothesize that individuals with deficient or inadequate vitamin D status, compared to individuals with adequate status, will be more likely to have AMD and DR and be more likely to develop AMD. The purpose of this proposal is to investigate associations between vitamin D status and both DR and AMD using data from the aging (45-64 years) Atherosclerosis Risk in Communities (ARIC) population-based, biracial (African American and Caucasian) cohort. We propose to use previously collected data, including graded retinal photographs for DR and AMD status, and assayed serum 25(OH)D concentrations from ARIC study participants collected from 1987-1995, as well as graded retinal photographs currently being obtained in a follow-up study (2011-2013). Specifically, we propose to investigate the association between vitamin D status, assessed at Visit 2 (1990-1992), and 1) the presence of DR assessed at Visit 3 (1993-1995) among 1,657 individuals with diabetes and 2) the presence of AMD assessed at Visit 3 (1993-1995) among 11,532 participants. Third, we also proposed to investigate, for the first time, the association between vitamin D status, assessed in 1990-1992, and the incidence or progression of AMD (from 1993-1995 to 2011-2013) in a sample of approximately 2,346 ARIC participants. This study will advance our understanding of vitamin D status in relation to common vision-threatening eye diseases in the elderly and could lead to new therapies for the prevention or reduced progression of these diseases.