AGE RELATED MACULOPATHY-DRUSEN BIOGENESIS

描述（来自申请人摘要的逐字描述）：视网膜相关黄斑 退行性变（AMD）的特征在于在视网膜中的视力的进行性丧失。 中央视野可归因于萎缩性、渗出性和/或出血性 黄斑的变化。AMD的标志之一是 视网膜色素上皮之间的细胞外沉积物，称为玻璃疣 (RPE)和它的血液供应脉络膜毛细血管在这个项目中，我们的工作 假设是特定的玻璃疣相关分子积累在 细胞质，或沿着基底表面，“受损”的RPE细胞提前 玻璃疣的形成因此，拟议研究的一个目的是 表征RPE在玻璃疣生物发生中的作用。第二，具有 证实了一些与玻璃疣相关的分子，事实上， 细胞来源的视网膜，视网膜色素上皮，和/或脉络膜，我们建议确定 这些局部细胞类型中的任何一种是否进行了重要的生物合成， 对玻璃疣的贡献。因此，我们建议确定相关细胞 类型，并确定这些与玻璃疣相关的分子中是否有任何一种 在玻璃疣或AMD个体中差异表达。微分 基因转录物在视网膜，RPE， 和脉络膜将使用自动荧光分析仪进行定量分析。 基于逆转录酶-聚合酶链反应的检测系统 （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以一种重要的方式 最终表现为AMD的一系列退行性变化。

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.