Kociok, Norbert, Crespo-Garcia, Sergio ORCID: 0000-0002-8640-9135, Liang, Yong, Klein, Sabrina V., Nuernberg, Christina, Reichhart, Nadine, Skosyrski, Sergej, Moritz, Eva, Maier, Anna-Karina, Brunken, William J., Strauss, Olaf, Koch, Manuel and Joussen, Antonia M. (2016). Lack of netrin-4 modulates pathologic neovascularization in the eye. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Netrins are a family of matrix-binding proteins that function as guidance signals. Netrin-4 displays pathologic roles in tumorigenesis and neovascularization. To answer the question whether netrin-4 acts either pro-or anti-angiogenic, angiogenesis in the retina was assessed in Ntn-4(-/-) mice with oxygeninduced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), mimicking hypoxiamediated neovascularization and inflammatory mediated angiogenesis. The basement membrane protein netrin-4 was found to be localised to mature retinal blood vessels. Netrin-4, but not netrin-1 mRNA expression, increased in response to relative hypoxia and recovered to normal levels at the end of blood vessel formation. No changes in the retina were found in normoxic Ntn-4(-/-) mice. In OIR, Ntn-4(-/-) mice initially displayed larger avascular areas which recovered faster to revascularization. Ganzfeld electroretinography showed faster recovery of retinal function in Ntn-4(-/-) mice. Expression of netrin receptors, Unc5H2 (Unc-5 homolog B, C. elegans) and DCC (deleted in colorectal carcinoma), was found in Muller cells and astrocytes. Laser-induced neovascularization in Nnt-4(-/-) mice did not differ to that in the controls. Our results indicate a role for netrin-4 as an angiogenesis modulating factor in O-2-dependent vascular homeostasis while being less important during normal retinal developmental angiogenesis or during inflammatory neovascularization.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kociok, NorbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crespo-Garcia, SergioUNSPECIFIEDorcid.org/0000-0002-8640-9135UNSPECIFIED
Liang, YongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, Sabrina V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reichhart, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Skosyrski, SergejUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moritz, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, Anna-KarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brunken, William J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strauss, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joussen, Antonia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-287582
DOI: 10.1038/srep18828
Journal or Publication Title: Sci Rep
Volume: 6
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OXYGEN-INDUCED RETINOPATHY; ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULARIZATION; VASCULAR DEVELOPMENT; RETINAL VASCULATURE; ANGIOGENESIS; EXPRESSION; MOUSE; IDENTIFICATION; MICEMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28758

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