Universität zu Köln

Nuernberg, Christina, Kociok, Norbert, Brockmann, Claudia, Lischke, Timo ORCID: 0000-0003-0413-4252, Crespo-Garcia, Sergio ORCID: 0000-0002-8640-9135, Reichhart, Nadine, Wolf, Susanne, Baumgrass, Ria ORCID: 0000-0002-3289-1608, Eming, Sabine A., Beer-Hammer, Sandra ORCID: 0000-0001-6049-0257 and Joussen, Antonia M. (2018). Myeloid cells contribute indirectly to VEGF expression upon hypoxia via activation of Miller cells. Exp. Eye Res., 166. S. 56 - 70. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1096-0007

Full text not available from this repository.

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 Muller 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 Muller cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nuernberg, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kociok, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Brockmann, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lischke, Timo UNSPECIFIED orcid.org/0000-0003-0413-4252 UNSPECIFIED Crespo-Garcia, Sergio UNSPECIFIED orcid.org/0000-0002-8640-9135 UNSPECIFIED Reichhart, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Baumgrass, Ria UNSPECIFIED orcid.org/0000-0002-3289-1608 UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beer-Hammer, Sandra UNSPECIFIED orcid.org/0000-0001-6049-0257 UNSPECIFIED Joussen, Antonia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-204389
DOI:	10.1016/j.exer.2017.10.011
Journal or Publication Title:	Exp. Eye Res.
Volume:	166
Page Range:	S. 56 - 70
Date:	2018
Publisher:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication:	LONDON
ISSN:	1096-0007
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; OXYGEN-INDUCED RETINOPATHY; VASCULAR-PERMEABILITY FACTOR; RETINAL NEOVASCULARIZATION; MULLER CELLS; INTRAVITREAL NEOVASCULARIZATION; OCULAR NEOVASCULARIZATION; PATHOLOGICAL ANGIOGENESIS; VITREAL MACROPHAGES; MOUSE RETINA Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20438