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Xiang Q. Werdich, Mariya Ali, Bela Anand-Apte; Vascular Endothelial Growth Factor-A Mediates Inflammatory Cell Recruitment in the Cornea. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2399.
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Vascular endothelial growth factor (VEGF)-A-mediated hemangiogenesis has been thought to cross-interact with tissue inflammatory responses. Corneal inflammation and lymphangiogenesis are associated with the termination of the immune-privileged state of the normally avascular cornea. Previous in vitro studies demonstrated that VEGF-A interacts with mononuclear phagocytes (MPs) at an affinity 20 times lower than that with endothelial cells, and is much less effective in stimulating MP chemotaxis. The goal of this study was to investigate corneal inflammatory responses resulting from VEGF-A exposure in vivo.
We measured the VEGF-A mediated recruitment of inflammatory cells in vivo using an established mouse corneal micropocket assay. Slow-release polymer-hydron-containing recombinant VEGF-A micropellets were implanted in adult mouse cornea (total of 100 ng per animal). Corneal tissue was harvested on days 1 to 7 post-VEGF implantation. Immunohistochemical analysis was performed on fresh-frozen corneal sections to demonstrate the recruitment of CD11b+ cells.
Exposure to 100 ng of recombinant VEGF-A in vivo induced marked corneal angiogenesis by day 7 following implantation. The number of CD11b+ macrophages in corneal stroma was significantly increased as early as 24 hours after implantation, while the influx persisted on day 7 post-implantation. We observed that VEGF-A mediated recruitment of inflammatory cells occurred in the absence of wound-induced corneal inflammation.
Our results indicate that VEGF-A causes tissue inflammation during pathological cornea neovascularization.
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