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: 7214704
• 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/7214704
• 关键词: Age; Age related macular degeneration; Aging; Alzheimer' s Disease; Apoptotic; Atherosclerosis; Bioinformatics; Blindness; Cell Death; Cells; Condition; Data; Dermal; Disease; Elderly; Epidemiologic Studies; Epithelium; Event; Eye; Failure; Functional disorder; Future; In Situ; Knowledge; Lead; Maps; Membranoproliferative Glomerulonephritis; Modality; Numbers; Oxidative Stress; Pathogenesis; Pathology; Pathway interactions; Patients; Phosphorylation; Photoreceptors; Population; Post-Translational Protein Processing; Proteins; Proteome; Proteomics; Pulmonary Emphysema; Research; Research Personnel; Retinal; Retinal Photoreceptors; Retinal Pigments; Risk Factors; Signal Transduction; Signal Transduction Pathway; Techniques; Tissues; Variant; Vascular Endothelium; Vision; Western World; age related; attenuation; cell type; glycation; improved; macula; oxidation; programs; protein expression; research study; response; stem; stressor

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(申请人提供)：老年性黄斑变性(AMD)是西方世界老年人口失明的主要原因。到目前为止，已尝试了几种“破坏性”治疗方法来改善AMD患者的中心视力，但均以失败告终。开发有效的治疗方法的失败源于我们对AMD发病机制的细胞机制了解不足。一些流行病学研究表明，年龄是AMD的主要危险因素。实验数据表明，糖基化、磷酸化或氧化对细胞蛋白质的翻译后修饰可能是年龄相关性视网膜细胞丢失的原因。然而，与年龄相关的视网膜细胞丢失和大体结构改变导致AMD的确切机制尚未确定。识别这些致病途径将有助于我们制定合理的策略来阻断导致AMD的细胞事件。建议的实验旨在确定(1)年轻(&lt；50)正常捐赠者、(2)没有任何视网膜病变的正常老年(&gt；65)捐赠者、(3)患有老年性黄斑病变(ARM)的老年捐赠者和(4)患有AMD的老年捐赠者黄斑和周边的RPE、脉络膜毛细血管和光感受器细胞的原位蛋白表达的差异。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。利用生物信息学技术，可能的病理事件和相关的路径将被识别。拟议的研究还将产生每个组织的地形图和与年龄相关的特定蛋白质组图，可用于该领域未来的研究。这一建议的结果无疑将提高我们对AMD细胞死亡的确切机制的理解，并有助于开发针对已识别的病理途径的更具体的治疗技术。

项目成果

Synthesis and secretion of hemoglobin by retinal pigment epithelium.

• DOI: 10.1167/iovs.07-1372
• 发表时间: 2009-04
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: T. Tezel;L. Geng;E. Lato;S. Schaal;Yongqing Liu;D. Dean;J. Klein;H. Kaplan

Retinal pigment epithelium rescues vascular endothelium from retinoic acid-induced apoptosis.

视网膜色素上皮将血管内皮从视黄酸诱导的细胞凋亡中拯救出来。

• DOI: 10.1167/iovs.05-1557
• 发表时间: 2006
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Tezel,TongalpH;Geng,Lijun;Kaplan,HenryJ;DelPriore,LucianV
• 通讯作者: DelPriore,LucianV