Proteomics of altered protein in macular degeneration

描述（由申请人提供）：目前，没有预防性治疗年龄相关性黄斑变性（AMD），这是美国老年人失明的主要原因。开发治疗干预措施将需要了解与疾病相关的分子事件。 在这项提案中，我们将测试一个假设，即一个子集的蛋白质将被独特地改变与AMD和AMD的进展将涉及蛋白质的变化，在临床上不同的功能表现的演变。这项研究将采用一种创新的分析方法，通过使用蛋白质组学技术来识别AMD患者感觉视网膜和视网膜色素上皮（RPE）中发生改变的特定蛋白质。选择的供体（年龄65-75）将包括表现出没有AMD（对照）或指示疾病的开始或后期阶段的视网膜特征的那些。本研究的主要目的是：（1）评价和分类供体眼的视网膜变性。在生化分析之前，我们将使用视网膜相关眼病（AREDS）系统评估供体眼睛的黄斑区域。(2)使用蛋白质组学分析鉴定视网膜蛋白质的改变。我们将进行蛋白质组分析，以确定蛋白质在视网膜色素上皮和感觉视网膜已改变表达或含有氧化修饰，4-羟基壬烯醛。在AMD的临床定义阶段使用供体视网膜应有助于区分与疾病进展相关的蛋白质变化模式。鉴定独特改变的蛋白质将有助于对AMD的机制提供有价值的见解。

DESCRIPTION (provided by applicant): Currently, there is no preventative treatment for age-related macular degeneration (AMD), the leading cause of blindness among the elderly in the U.S.. Development of therapeutic interventions will require an understanding of the molecular events associated with the disease. In this proposal, we will test the hypothesis that a subset of proteins will be uniquely altered with AMD and that the progression of AMD will involve an evolution of protein changes that are manifest in clinically distinct features. This research will take an innovative analytical approach by using proteomic technology to identify specific proteins that are altered in the sensory retina and retinal pigment epithelium (RPE) with AMD. Donors selected (ages 65-75) will include those exhibiting either no AMD (control) or retinal features that are indicative of the beginning or later stages of the disease. The following aims will be pursued: (1) Evaluate and classify retinal degeneration in donor eyes. Prior to biochemical analysis, we will evaluate the macular region of donor eyes using the Age-related Eye Disease (AREDS) system. (2) Identify alterations in retinal proteins using proteomic analysis. We will perform proteome analysis to identify proteins in the RPE and sensory retina that have altered expression or contain the oxidative modification, 4-hydroxynonenal. Using donor retinas at clinically defined stages of AMD should aid in distinguishing patterns of protein changes that are associated with the progression of the disease. Identification of proteins that are uniquely altered will help provide valuable insight into the mechanism of AMD.