Universität zu Köln

Lueckoff, Anika, Caramoy, Albert, Scholz, Rebecca, Prinz, Marco, Kalinke, Ulrich ORCID: 0000-0003-0503-9564 and Langmann, Thomas (2016). Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization. EMBO Mol. Med., 8 (6). S. 670 - 679. HOBOKEN: WILEY. ISSN 1757-4684

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Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon- signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon-/ receptor (Ifnar) using Ifnar1(-/-) mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser-treated Cx3cr1(CreER):Ifnar1(fl/fl) animals that allowed the tamoxifen-induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN- therapy of laser-treated wild-type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN- therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lueckoff, Anika UNSPECIFIED UNSPECIFIED UNSPECIFIED Caramoy, Albert UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Prinz, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalinke, Ulrich UNSPECIFIED orcid.org/0000-0003-0503-9564 UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-274406
DOI:	10.15252/emmm.201505994
Journal or Publication Title:	EMBO Mol. Med.
Volume:	8
Number:	6
Page Range:	S. 670 - 679
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1757-4684
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; MICROGLIA; CELLS; INFLAMMATION; MACROPHAGES; PROGRESS; THERAPY Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27440