Retina/RPE genes altered in aging as candidates for AMD

描述（由申请人提供）：视网膜相关性黄斑变性（AMD）是 老年人视力丧失的主要原因。病因 AMD的发病机制是复杂的，似乎涉及遗传和环境因素。 成分AMD的具体原因尚不清楚。年龄的增长也许是 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）和布鲁赫氏 膜使一些个体易于随后发展为AMD。几 细胞途径可能涉及AMD的病理生物学。两种途径 特别提示在AMD发病机制中起作用的是： 氧化应激和脂质/胆固醇代谢。这项提案的目的是 以确定候选基因并检查它们对AMD的贡献 易感性这项研究的假设是：a）视网膜老化， RPE的特征在于基因表达的变化，和B）基因，其 在衰老过程中表达水平改变的基因可能包括 有助于AMD易感性。具体目的是：1）检测基因 人视网膜和RPE在衰老过程中的表达谱。表达谱 将在年轻人和老年人对照组之间进行比较。特别是， 与年龄相关的基因表达的变化，参与对氧化应激的反应， 将分析压力和脂质/胆固醇代谢。2)以识别 候选基因，并检查它们对AMD的贡献。AMD之间的关系 易感性和基因，其表达水平被发现改变 将在641名AMD患者和112名 对照

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.