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A. Oyejide, C. Ghosn, N. Linke, T. Lin, J. Burke; Pro-inflammatory Response to Intravitreal hrVEGF in the Retina: An Immunoassay and Immunohistological Evaluation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3600.
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Two non-human primates were injected intravitreally with 1.25 ug / 50ul VEGF and a third served as the naïve control. Animals were enucleated at Day 3 or Day 7 after VEGF injection. Retinal pro-inflammatory factor release was assessed by two methods: 1) immunohistological analysis and 2) Luminex panel of antigens, inflammatory cytokines, chemokines, growth factors, and other cellular markers.
VEGF caused profound histological alterations of the retina characterized by foveal edema, segmental retinal detachment, hemorrhage, transient pigmentation and cellular infiltration. Most infiltrating cells were myeloperoxidase (MPO)-reactive polymorphonuclear neutrophils in focal areas of the retina at day 3, but which were absent by day 7. Concurrently, MPO and IL-8 levels increased significantly in homogenized retinal tissue at day3 but returned to near normal by day 7. Sparse CD-3+ T cells and even fewer CD-68+ macrophages were present in the retina only at day 7. These changes were accompanied by significantly increased levels of MCP-1 IL-1ra, MIP-1beta, IFN-gamma, IL-16, IL-1beta, PAI-1 TNF-RII and endothelin at day 3, with reduced levels by day 7.
VEGF caused acute retinal inflammation associated with infiltration of predominantly MPO-reactive neutrophils and moderate expression of several proinflammatory proteins, including MPO and IL-8.
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