Proteomics of altered protein in macular degeneration

描述（由申请人提供）：目前，年龄相关性黄斑变性（AMD）是美国老年人失明的主要原因，没有预防性治疗方法。治疗干预措施的发展将需要了解与疾病相关的分子事件。在这一提议中，我们将验证一种假设，即一组蛋白质将在AMD中发生独特的改变，并且AMD的进展将涉及蛋白质变化的进化，这些变化在临床不同的特征中表现出来。本研究将采用一种创新的分析方法，利用蛋白质组学技术鉴定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。选择的捐赠者（65-75岁）将包括那些没有AMD（对照）或显示该疾病初期或后期的视网膜特征的人。以下目标将被追求：(1)评估和分类视网膜退化供体的眼睛。在生化分析之前，我们将使用年龄相关眼病（AREDS）系统评估供体眼睛的黄斑区域。(2)利用蛋白质组学分析确定视网膜蛋白的改变。我们将进行蛋白质组学分析，以鉴定RPE和感觉视网膜中表达改变或含有氧化修饰的4-羟基壬烯醛的蛋白质。在临床上确定的AMD阶段使用供体视网膜应该有助于区分与疾病进展相关的蛋白质变化模式。鉴定被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.