Characterization of novel genes expressed in the retinal pigment epithelium (RPE) and assessment of their role in age-related macular degeneration

在工业化国家，年龄相关性黄斑变性（AMD）是导致法定失明的最常见原因，主要影响75岁以上的老年人。它与视网膜色素上皮（RPE）产生的细胞外碎片组成的囊肿的形成密切相关。虽然AMD发病机制的主要事件尚不清楚，但人们普遍认为，高代谢RPE的恶化导致黄斑变性。RPE是一个单层细胞，在持续支持和更新杆状和锥状光感受器中起着至关重要的作用。为了实现这些功能，RPE被认为需要大量的蛋白质，其中一些可能是这种细胞类型所特有的。尽管它在正常的眼部代谢和疾病中具有重要意义，但对RPE功能和功能障碍的生化基础知之甚少。因此，我们项目的目的是鉴定和表征在RPE中特异性或丰富表达的基因。此外，我们计划在一组明确定义的AMD患者以及种族和年龄匹配的对照个体中寻找这些基因的序列变化。本研究有望有助于我们了解RPE功能的遗传基础，并阐明RPE相关基因在AMD易感性中的作用。

Age-related macular degeneration (AMD) is the most common cause of legal blindness in industrialized countries and predominantly affects the elderly population over 75 years of age. It is intimately related to the formation of drusen that consist of extracellular debris produced by the retinal pigment epithelium (RPE). Although the primary events in AMD pathogenesis are not well understood, it is generally agreed that the deterioration of the highly metabolic RPE gives rise to macular degeneration. The RPE is a single layer of cells that play a crucial role in the continual support and renewal of the rod and cone photoreceptors. To carry out these functions, the RPE is thought to require a large number of proteins some of which may be unique to this cell type. Despite its outstanding importance in normal ocular metabolism and disease, little is known about the biochemical basis of RPE function and dysfunction. It is therefore the aim of our project to identify and characterize genes specifically or abundantly expressed in the RPE. In addition, we plan to search for sequence variations in these genes in a well-defined group of AMD patients and ethnically and agematched controll individuals. This study is expected to contribute to our understanding of the genetic basis of RPE function and to clarify the role of RPE-related genes in the predisposition to AMD.