IN VIVO ROLE OF CAVEOLIN-1 IN MODULATING PHOTORECEPTOR FUNCTION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 血视网膜屏障（BRB）选择性地和紧密地调节神经视网膜的局部环境。BRB完整性的丧失是三种主要致盲原因的常见病理学：糖尿病视网膜病变;年龄相关性黄斑变性;和早产儿视网膜病变。最近的证据表明，小窝蛋白-1（Cav-1）是必不可少的正常视网膜功能和BRB的完整性和Cav-1的表达变化，以响应实验性糖尿病。Cav-1缺失小鼠通过视网膜电图显示出视网膜功能降低，这不能通过Cav-1在光感受器中的特异性丧失来解释。因此，Cav-1缺失视网膜的功能缺陷可能是由光感受器周围的异常局部环境引起的。为了支持这一假设，Cav-1缺失小鼠显示出明显的血-视网膜屏障性质丧失、视网膜功能降低和视网膜中离子稳态破坏。我们目前正在研究条件性细胞特异性敲除Cav-1，以确定介导Cav-1依赖性视网膜功能丧失的细胞类型。我们最初的COBRE子项目的目标是研究Cav-1调节BRB完整性的机制。这些目标与我们最近获得的R 01应用一致。因此，我们已经扩大了我们的COBRE支持的项目，以开发一个新的研究方向，涉及正常和病理视网膜血管的蛋白质组图谱的生成。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The blood-retinal barrier (BRB) selectively and tightly regulates the local environment of the neural retina. Loss of BRB integrity is a common pathology in three major causes of blindness: diabetic retinopathy; age-related macular degeneration; and retinopathy of prematurity. Recent evidence indicates that caveolin-1 (Cav-1) is essential for normal retinal function and BRB integrity and that Cav-1 expression changes in response to experimental diabetes. Cav-1 null mice display reduced retinal function by electroretinography that cannot be explained by loss of Cav-1 specifically in photoreceptors. Thus, the functional deficit in Cav-1 null retinas likely results from an abnormal local environment surrounding photoreceptors. In support of this hypothesis, Cav-1 null mice display a clear loss of blood-retinal barrier properties, reduced retinal function, and disruption of ion homeostasis in the retina. We are currently examining conditional cell-specific knockouts of Cav-1 to determine the cell type that mediates Cav-1 dependent loss of retinal function. The goals of our original COBRE subproject were to examine the mechanism(s) by which Cav-1 regulates BRB integrity. These goals were aligned with our recently awarded R01 application. As a result, we have expanded our COBRE supported project to develop a new direction of research involving the generation of proteome maps of normal and pathological retinal vasculature.