Universität zu Köln

Semkova, Irma, Kociok, Norbert, Karagiannis, Dimitrios, Nischt, Roswitha, Smyth, Neil, Paulsson, Mats, Strauss, Olaf ORCID: 0000-0002-6272-8596 and Joussen, Antonia M. (2014). Anti-angiogenic effect of the basement membrane protein nidogen-1 in a mouse model of choroidal neovascularization. Exp. Eye Res., 118. S. 80 - 89. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1096-0007

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Abstract

In patients with age-related macular degeneration disruption of the integrity of the retinal pigment epithelium (RPE) and Bruch's membrane (BrM), precedes choroidal neovascularization (CNV). We investigated the role of the basement membrane (BM) proteins nidogen-1 and nidogen-2 for the development of experimental CNV. Laser-induced CNV was studied in Nid1(-/-) and Nid2(-/-) mice and wild type (WT) controls by fluorescein angiography, by immune histochemistry of flat-mounts or paraffin sections to analyze expression pattern of nidogen-1 and -2 and nidogen binding BM proteins, and by western blotting. The influence of VEGF and bFGF on the mRNA expression of nidogen-1 was studied in vitro. Nidogen-1 protein is present in the BM of the inner limiting membrane (ILM), the retinal capillaries, and the choroid/sclera and CNV. Nidogen-2 protein is also found in these BMs but with a weaker expression in the ILM. In the retina the absence of nidogen-1 does not influence the expression of nidogen-2 and vice versa and does not influence the expression of the BM components collagen IV, laminin gamma 1, and perlecan. In Nid(-/-) mice, CNV lesions showed increased vessel leakage during angiography and the CNV area was larger than in WT or nidogen-2 deficient mice. Laser treatment led to up-regulation of nidogen-1 protein expression in the sclera/choroid of nidogen-2 deficient or WT mice. The treatment of HUVECs with VEGF leads to a reduced expression of nidogen-1 mRNA whereas its expression remained unchanged in RPE cells. In conclusion, nidogen-1 produced by the endothelial cells acts as a factor to help stabilizing the BM, thus preventing the sprouting of new vessels or the infiltration of endothelial cells. In this sense nidogen-1 is essential to provide an anti-angiogenic environment of differentiated vessels. (C) 2013 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Semkova, Irma UNSPECIFIED UNSPECIFIED UNSPECIFIED Kociok, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Karagiannis, Dimitrios UNSPECIFIED UNSPECIFIED UNSPECIFIED Nischt, Roswitha UNSPECIFIED UNSPECIFIED UNSPECIFIED Smyth, Neil UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Strauss, Olaf UNSPECIFIED orcid.org/0000-0002-6272-8596 UNSPECIFIED Joussen, Antonia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-451015
DOI:	10.1016/j.exer.2013.11.006
Journal or Publication Title:	Exp. Eye Res.
Volume:	118
Page Range:	S. 80 - 89
Date:	2014
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 LEUKOCYTE RESPONSE INTEGRIN; COLLAGEN TYPE-IV; MACULAR DEGENERATION; BINDING; LAMININ; ENTACTIN; NETWORK; CELLS; GENE; MICE Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45101