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:
CreatorsEmailORCIDORCID Put Code
Lueckoff, AnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caramoy, AlbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scholz, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prinz, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kalinke, UlrichUNSPECIFIEDorcid.org/0000-0003-0503-9564UNSPECIFIED
Langmann, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; MICROGLIA; CELLS; INFLAMMATION; MACROPHAGES; PROGRESS; THERAPYMultiple languages
Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27440

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