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

Nuernberg, C.; Kociok, N.; Brockmann, C.; Lischke, T.; Crespo-Garcia, S.; Reichhart, N.; Wolf, S.; Baumgrass, R.; Eming, S.A.; Beer-Hammer, S.; Joussen, A.M.

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

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Item Type:	Article
Title:	Myeloid cells contribute indirectly to VEGF expression upon hypoxia via activation of Müller cells
Creators Name:	Nuernberg, C., Kociok, N., Brockmann, C., Lischke, T., Crespo-Garcia, S., Reichhart, N., Wolf, S., Baumgrass, R., Eming, S.A., 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
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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