Retina/RPE genes altered in aging as candidates for AMD

描述(申请人提供)：老年性黄斑变性(AMD) 是导致老年人不可逆转视力丧失的主要原因。病因学 AMD的发病是复杂的，似乎既涉及遗传因素，也涉及环境因素 组件。老年性黄斑变性的具体原因(S)尚不清楚。高龄或许就是 最重要的风险因素。因此，必须了解如何 视网膜、视网膜色素上皮(RPE)和Bruch‘s的年龄相关性变化 膜使一些个体易患AMD的后续发展。几个 细胞通路可能参与了AMD的病理生物学过程。两条路 已经明确提出在AMD发病机制中发挥作用的有： 氧化应激和脂质/胆固醇代谢。这项提议的目标是 确定候选基因并研究它们对AMD的影响 敏感度。这项研究的假设是a)视网膜老化和 RPE的特征是基因表达的变化，以及b)其 在衰老过程中表达水平改变可能包括特定的基因 增加AMD的易感性。具体目标是：1)检测基因 衰老过程中人视网膜和视网膜色素上皮的表达谱。表达简档 将在年轻人和老年对照组之间进行比较。特别是， 氧化反应相关基因表达的增龄性变化 将分析压力和脂肪/胆固醇代谢。2)识别 候选基因并研究它们对AMD的贡献。AMD之间的联系 易感性和基因，其表达水平被发现发生变化 在衰老过程中保持一致，将在641名AMD患者和112名AMD患者中进行探索 控制。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly. The etiology of AMD is complex and appears to involve both a genetic and an environmental component. The specific cause(s) of AMD are not known. Advancing age is perhaps the most important risk factor. Thus it is essential to understand how age-related changes in the retina, retinal pigment epithelium (RPE) and Bruch's membrane predispose some individuals to subsequent development of AMD. Several cellular pathways are likely involved in the pathobiology of AMD. Two pathways that have specifically been suggested to play a role in AMD pathogenesis are: oxidative stress and lipid/cholesterol metabolism. The goal of this proposal is to identify candidate genes and examine their contribution to AMD susceptibility. The hypotheses of this study are a) aging of the retina and the RPE is characterized by changes in gene expression, and b) genes whose expression levels are altered during aging may include genes that specifically contribute to AMD susceptibility. The specific aims are: 1) To examine gene expression profiles in human retina and RPE during aging. Expression profiles will be compared between young adults and elderly controls. In particular, age-related changes in expression of genes involved in response to oxidative stress and lipid/cholesterol metabolism will be analyzed. 2) To identify candidate genes and examine their contribution to AMD. Associations between AMD susceptibility and genes, whose expression levels were found to change consistently during aging, will be explored in 641 AMD patients and 112 controls.