AGE RELATED MACULOPATHY-DRUSEN BIOGENESIS

年龄相关性黄斑病-玻璃疣生物发生

• 批准号: 6635653
• 负责人: DON H ANDERSON
• 金额: $ 32.85万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635653
• 关键词: acute phase protein; aging; apoptosis; cell type; cellular pathology; choroid uvea; clinical research; complement pathway; confocal scanning microscopy; gene expression; human subject; immunocytochemistry; immunoelectron microscopy; inflammation; macrophage; macular degeneration; macular drusen; messenger RNA; molecular pathology; polymerase chain reaction; protein biosynthesis; retinal pigment epithelium; tissue /cell culture; uvea disorder; vision disorders

DESCRIPTION (Verbatim from applicant's abstract): Age-related macular degeneration (AMD) is characterized by the progressive loss of vision in the central visual field attributable to atrophic, exudative and/or hemorrhagic changes in the macula. One of the hallmarks of AMD is the accumulation of extracellular deposits known as drusen between the retinal pigmented epithelium (RPE) and its blood supply, the choriocapillaris. In this project, our working hypothesis is that specific drusen-associated molecules accumulate in the cytoplasm, or along the basal surface, of "compromised" RPE cells in advance of actual drusen formation. One aim of the proposed research, therefore, is to characterize the role of the RPE in drusen biogenesis. Secondly, having confirmed that a number of drusen-associated molecules do, in fact, have local cellular sources in the retina, RPE, and/or choroid, we propose to determine whether any of these local cell types make a significant biosynthetic contribution to drusen. Accordingly, we propose to identify the relevant cell types, and to determine whether any of these drusen-associated molecules are expressed differentially in individuals with drusen or AMD. Differential expression of gene transcripts in target tissues [cells] in the retina, RPE, and choroid will be analyzed quantitatively using an automated fluorogenic detection system based upon the reverse transcriptase-polymerase chain reaction (RT-PCR). In pursuing these studies, we hope to determine whether changes in the expression of one or more of these genes contributes in a significant way to the cascade of degenerative changes that ultimately manifests itself as AMD.

描述(逐字摘自申请者摘要)：老年性黄斑 退行性变(AMD)的特征是进行性视力丧失 中央视野可归因于萎缩、渗出和/或出血 黄斑的变化。AMD的特征之一是积累了 视网膜色素上皮之间的称为玻璃体的细胞外沉积 (RPE)及其血液供应，脉络膜毛细血管。在这个项目中，我们的工作 假说是特定的与干酪蛋白相关的分子在 “受损”的RPE细胞的细胞质或沿基底面。 实实在在的泥浆地层。因此，拟议研究的一个目的是 描述RPE在玻璃疱疹生物发生中的作用。第二，拥有 证实了事实上，一些与干酪蛋白相关的分子确实具有局部 视网膜、RPE和/或脉络膜中的细胞来源，我们建议确定 这些局部细胞类型中的任何一种都是显著的生物合成 对干酪的贡献。因此，我们建议确定相关的单元 类型，并确定这些与干酪蛋白相关的分子中是否有 在红斑狼疮或AMD患者中表达不同。差动 基因转录产物在靶组织[细胞]中的表达，视网膜，RPE， 脉络膜将使用自动荧光分析仪进行定量分析 基于逆转录聚合酶链式反应的检测系统 (RT-PCR)。在进行这些研究时，我们希望确定 这些基因中的一个或多个的表达在很大程度上有助于 最终表现为AMD的一连串退行性变化。

项目成果

Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration:: Characterization, ethnic distribution and evolutionary implications

• DOI: 10.1080/07853890601097030
• 发表时间: 2006-01-01
• 期刊: ANNALS OF MEDICINE
• 影响因子: 4.4
• 作者: Hageman, Gregory S.;Hancox, Lisa S.;Dean, Michael
• 通讯作者: Dean, Michael

Vitronectin gene expression in the adult human retina.

玻连蛋白基因在成人视网膜中的表达。

• 发表时间: 1999
• 期刊: Investigative ophthalmology & visual science.
• 作者: Anderson,DH;Hageman,GS;Mullins,RF;Neitz,M;Neitz,J;Ozaki,S;Preissner,KT;Johnson,LV
• 通讯作者: Johnson,LV