PROTEOMIC ANALYSIS OF AGE-RELATED MACULAR DEGENERATION

年龄相关性黄斑变性的蛋白质组学分析

• 批准号: 7037396
• 负责人: TONGALP H TEZEL
• 金额: $ 14.85万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037396
• 关键词: aging; bioinformatics; cell cycle proteins; glycation; human tissue; macular degeneration; oxidation; phosphorylation; posttranslational modifications; proteomics; retinal pigment epithelium; two dimensional gel electrophoresis; visual photoreceptor

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population in the Western world. So far, several "destructive" treatment modalities have been tried in vain to improve the central vision in patients with AMD. The failure of developing effective treatment stems from the inadequacy of our knowledge of cellular mechanisms in AMD pathogenesis. Several epidemiological studies indicate aging as the predominant risk factor for AMD. Experimental data suggest that post-translational modifications of cellular proteins by glycation, phosphorylation or oxidation may be responsible for age related retinal cell loss. However, the exact mechanisms involved in age-related retinal cell loss and macrostructural alterations leading to AMD have not yet been identified. Identification of these pathogenetic pathways will help us to develop rational strategies to block the cellular events leading to AMD. Proposed experiments aim to identify the differential in situ protein expressions of RPE, choriocapillaris and photoreceptor cells in the macula and periphery of the (1) young (<50) normal donors, (2) normal old (>65) donors without any retinal pathology, (3) old donors with age-related maculopathy (ARM), and (4) old donors with AMD. Comparison of these proteome maps will reveal the topographical and age-related variations in protein expression of each cell type. Such proteome maps will also be useful in detecting the differentially expressed proteins in ARM and in AMD. Using bioinformatic techniques, possible pathological events and related pathways will be identified. Proposed studies will also yield topographical and age-correlated specific proteome maps of each tissue which can be used for future research in the field. Results of this proposal will undoubtedly improve our understanding of the precise mechanisms of cell death in AMD and facilitate efforts to develop more specific treatment techniques aimed at identified pathological pathways.

描述（由申请人提供）：视网膜相关性黄斑变性（AMD）是西方世界老年人群失明的主要原因。到目前为止，几种“破坏性”的治疗方式已经尝试过徒劳地改善AMD患者的中心视力。开发有效治疗的失败源于我们对AMD发病机制的细胞机制的认识不足。一些流行病学研究表明，老龄化是AMD的主要危险因素。实验数据表明，通过糖化、磷酸化或氧化的细胞蛋白质的翻译后修饰可能是与年龄相关的视网膜细胞损失的原因。然而，与年龄相关的视网膜细胞丢失和宏观结构改变导致AMD的确切机制尚未确定。识别这些发病途径将帮助我们制定合理的策略来阻止导致AMD的细胞事件。提出的实验旨在鉴定（1）年轻（<50）正常供体、（2）没有任何视网膜病理的正常老年（>65）供体、（3）患有年龄相关性黄斑病变（ARM）的老年供体和（4）患有AMD的老年供体的黄斑和外周中RPE、脉络膜毛细血管和感光细胞的差异原位蛋白表达。这些蛋白质组图谱的比较将揭示每种细胞类型的蛋白质表达的地形和年龄相关的变化。这种蛋白质组图谱也将有助于检测ARM和AMD中差异表达的蛋白质。使用生物信息学技术，将确定可能的病理事件和相关途径。拟议的研究还将产生每个组织的地形和年龄相关的特定蛋白质组图，可用于该领域的未来研究。这一建议的结果无疑将提高我们对AMD细胞死亡确切机制的理解，并促进开发针对已确定病理途径的更具体治疗技术的努力。