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Christine M. Sorenson, Juliana Falero-Perez, Nader Sheibani; Bim Expression Modulates Retinal Astrocyte Function through Regulation of the Extracellular Microenvironment. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6018.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal astrocytes act as an intermediary between neural and vascular cells facilitating retinal vascular development and remodeling while maintaining normal function and neuronal integrity. We previously showed that Bim deficient mice (Bim -/-) were protected from hyperoxia mediated vessel obliteration and ischemia-mediated neovascularization. Here we assessed how lack of Bim expression in retinal astrocytes affects their function.
Retinal astrocytes were prepared from Bim +/+ and Bim -/- mice using a method we described previously. Isolated retinal astrocytes were subjected to transwell and scratch wound migration assays, and their ability to undergo morphogenesis was determined by plating on Matrigel. Conditioned medium from astrocytes was analyzed for production of various extracellular matrix proteins by Western blotting. The vascular endothelial growth factor (VEGF) level in astrocytes was determined by ELISA. The ability of cells to adhere to various matrix proteins was also investigated.
Astrocytes lacking Bim expression demonstrated decreased migration, an inability to undergo morphogenesis in Matrigel, and aberrant adhesion to various extracellular matrix proteins. Bim deficient astrocytes had reduced expression of TSP1 but increased expression of osteopontin, SPARC and VEGF.
Expression of the pro-apoptotic protein Bim not only modulates the extracellular matrix milieu and VEGF expression but also as a consequence affects astrocyte migration and morphogenesis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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