IN VIVO ROLE OF CAVEOLIN-1 IN MODULATING PHOTORECEPTOR FUNCTION

University Of Oklahoma Hlth Sciences Ctr, Oklahoma City OK

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Abstract

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.