Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.
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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-β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD Complete deletion of interferon-α/β 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(Cre) (ER):Ifnar1(fl/fl) animals that allowed the tamoxifen-induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN-β 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-β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD.
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| Authors | Anika Lückoff, Albert Caramoy, Rebecca Scholz, Marco Prinz, Ulrich Kalinke, Thomas Langmann |
| Journal | EMBO molecular medicine (EMBO Mol Med) Vol. 8 Issue 6 Pg. 670-8 (06 2016) ISSN: 1757-4684 [Electronic] England |
| PMID | 27137488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2016 The Authors. Published under the terms of the CC BY 4.0 license. |
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