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Myeloid cells contribute indirectly to VEGF expression upon hypoxia via activation of Müller cells

Item Type:Article
Title:Myeloid cells contribute indirectly to VEGF expression upon hypoxia via activation of Müller cells
Creators Name:Nuernberg, C. and Kociok, N. and Brockmann, C. and Lischke, T. and Crespo-Garcia, S. and Reichhart, N. and Wolf, S. and Baumgrass, R. and Eming, S.A. and Beer-Hammer, S. and Joussen, A.M.
Abstract:Anti-VEGF-directed therapies have been a milestone for treating retinal vascular diseases. Depletion of monocyte lineage cells suppresses pathological neovascularization in the oxygen-induced retinopathy mouse model. However, the question whether myeloid-derived VEGF-A expression is responsible for the pathogenesis in oxygen-induced retinopathy remained unknown. We analyzed LysMCre-driven myeloid cell-specific VEGF-A knockout mice as well as mice with complete depletion of circulating macrophages through clodronate-liposome treatment in the oxygen-induced retinopathy model by immunohistochemistry, qPCR, and flow cytometry. Furthermore, we analyzed VEGF-A mRNA expression in MIO-M1 cells alone and in co-culture with BV-2 cells in vitro. The myeloid cell-specific VEGF-A knockout did not change relative retinal VEGF-A mRNA levels, the relative avascular area or macrophage/granulocyte numbers in oxygen-induced retinopathy and under normoxic conditions. We observed an insignificantly attenuated pathology in systemically clodronate-liposome treated knockouts but evident VEGF-A expression in activated Müller cells on immunohistochemically stained sections. MIO-M1 cells had significantly higher expression levels of VEGF-A in co-culture with BV-2 cells compared to cultivating MIO-M1 cells alone. Our data show that myeloid-derived cells contribute to pathological neovascularization in oxygen-induced retinopathy through activation of VEGF-A expression in Müller cells.
Keywords:VEGF, Oxygen Induced Retinopathy, Myeloid Derived Cells, Macrophages, Microglia Cells, Animals, Mice
Source:Experimental Eye Research
ISSN:0014-4835
Publisher:Elsevier / Academic Press (U.S.A.)
Volume:166
Page Range:56-69
Date:January 2018
Official Publication:https://doi.org/10.1016/j.exer.2017.10.011
PubMed:View item in PubMed

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