CYP1B1 and Retinal Astrocyte Function

University Of Wisconsin-Madison, Madison WI

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Abstract

Project Summary/Abstract This F31-Diversity Application provides a detailed training plan for Juliana M Falero Perez to fulfill her professional career goals of completing her PhD degree, transition into a high-level postdoc position, and become an independent researcher. Her training plan identifies areas of mentorship and training such as: writing manuscripts and grants, 2) professional networking, 3) Teaching/Mentorship and leadership. Her scientific project is funded by her sponsor's Nader Sheibani NIH grants R24 EY022883 and R01 EY026078, and other grants that relate to ocular neovascularization and the role endogenous inhibitors of angiogenesis play in ocular vascular homeostasis and various eye diseases with a neovascular component. Our laboratory recently showed that Cyp1b1 is expressed in vascular cells from vascular bed of different tissues including retina. We also showed Cyp1b1 plays a significant role during postnatal development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Although we have demonstrated the cell autonomous impact of Cyp1b1 deficiency on retinal vascular cells, we know little about the physiological role of Cyp1b1 expression in retinal astrocyte function. Furthermore, it is not clear whether expression of Cyp1b1 in endothelial cells, pericytes, and/or astrocytes is responsible for ischemia-mediated retinal neovascularization. Astrocytes are the most abundant cells in the central nervous system including the retina. Their functions range from secretion or absorption of neural transmitters to maintenance of the blood-brain or blood-retina barrier. Astrocyte dysfunction could contribute to various pathologies including diabetic retinopathy and various neurological disorders. Our interest in retinal astrocytes comes from its critical role during normal inner retinal vascularization and degeneration of retinal astrocytes in ischemic retina with damage to the blood retinal barrier in retinopathy of prematurity. In fact, astrocytes are the major source of the matricellular proteins thrombospondins-1 and-2 (TSP1 and TSP2) that have significant roles in neuronal synaptogenesis, as well as regulation of angiogenesis. The studies proposed here will address the cell autonomous impact of Cyp1b1 expression in retinal astrocytes function in culture, as well retinal vascular development and neovascularization, using vascular cell specific targeted deletion of Cyp1b1, in vivo. These studies will advance our understanding of the molecular and cellular mechanisms acting through Cyp1b1 that contribute to retinal neurovascular development, angiogenesis, and function. Project Summary/Abstract Page: