IN VIVO ROLE OF CAVEOLIN-1 IN MODULATING PHOTORECEPTOR FUNCTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 血-视网膜屏障(BRB)选择性地、紧密地调节神经视网膜的局部环境。BRB完整性的丧失是导致失明的三个主要原因的常见病理：糖尿病视网膜病变、老年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)对于正常的视网膜功能和BRB的完整性是必不可少的，并且Cav-1的表达随着实验性糖尿病的反应而改变。CAV-1基因缺失的小鼠通过视网膜电描记术表现出视网膜功能下降，这不能用光感受器中CAV-1的丢失来解释。因此，Cav-1缺失视网膜的功能缺陷可能是由于光感受器周围的局部环境异常所致。为了支持这一假说，Cav-1基因缺失的小鼠表现出明显的血-视网膜屏障特性丧失，视网膜功能降低，视网膜离子动态平衡被破坏。我们目前正在研究Cav-1的条件性细胞特异性基因敲除，以确定介导Cav-1依赖的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(S)。这些目标与我们最近授予的R01申请一致。因此，我们扩大了我们的Cobre支持项目，以开发一个新的研究方向，包括生成正常和病理视网膜血管的蛋白质组图。

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.