Universität zu Köln

Karlstetter, Marcus, Kopatz, Jens, Aslanidis, Alexander, Shahraz, Anahita, Caramoy, Albert, Linnartz-Gerlach, Bettina ORCID: 0000-0003-4485-684X, Lin, Yuchen, Lueckoff, Anika, Fauser, Sascha, Dueker, Katharina, Claude, Janine, Wang, Yiner, Ackermann, Johannes, Schmidt, Tobias ORCID: 0000-0003-3102-3515, Hornung, Veit ORCID: 0000-0002-4150-194X, Skerka, Christine, Langmann, Thomas and Neumann, Harald ORCID: 0000-0002-5071-5202 (2017). Polysialic acid blocks mononuclear phagocyte reactivity, inhibits complement activation, and protects from vascular damage in the retina. EMBO Mol. Med., 9 (2). S. 154 - 167. HOBOKEN: WILEY. ISSN 1757-4684

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Abstract

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly population. Its pathophysiology is linked to reactive oxygen species (ROS) and activation of the complement system. Sialic acid polymers prevent ROS production of human mononuclear phagocytes via the inhibitory sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC11) receptor. Here, we show that low-dose intravitreal injection of low molecular weight polysialic acid with average degree of polymerization 20 (polySia avDP20) in humanized transgenic mice expressing SIGLEC11 on mononuclear phagocytes reduced their reactivity and vascular leakage induced by laser coagulation. Furthermore, polySia avDP20 prevented deposition of the membrane attack complex in both SIGLEC11 transgenic and wild-type animals. In vitro, polySia avDP20 showed two independent, but synergistic effects on the innate immune system. First, polySia avDP20 prevented tumor necrosis factor-, vascular endothelial growth factor A, and superoxide production by SIGLEC11-positive phagocytes. Second, polySia avDP20 directly interfered with complement activation. Our data provide evidence that polySia avDP20 ameliorates laser-induced damage in the retina and thus is a promising candidate to prevent AMD-related inflammation and angiogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Karlstetter, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Kopatz, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Aslanidis, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Shahraz, Anahita UNSPECIFIED UNSPECIFIED UNSPECIFIED Caramoy, Albert UNSPECIFIED UNSPECIFIED UNSPECIFIED Linnartz-Gerlach, Bettina UNSPECIFIED orcid.org/0000-0003-4485-684X UNSPECIFIED Lin, Yuchen UNSPECIFIED UNSPECIFIED UNSPECIFIED Lueckoff, Anika UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Dueker, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Claude, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Yiner UNSPECIFIED UNSPECIFIED UNSPECIFIED Ackermann, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Tobias UNSPECIFIED orcid.org/0000-0003-3102-3515 UNSPECIFIED Hornung, Veit UNSPECIFIED orcid.org/0000-0002-4150-194X UNSPECIFIED Skerka, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumann, Harald UNSPECIFIED orcid.org/0000-0002-5071-5202 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-240399
DOI:	10.15252/emmm.201606627
Journal or Publication Title:	EMBO Mol. Med.
Volume:	9
Number:	2
Page Range:	S. 154 - 167
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1757-4684
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; MICROGLIAL CELLS; EPITHELIAL-CELLS; HUMAN SIGLEC-11; C3 CONVERTASE; MACROPHAGES; NEUROTOXICITY; VISUALIZATION; MECHANISMS Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24039