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Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.


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(Cre) (ER):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.

SUBMITTER: Luckoff A 

PROVIDER: S-EPMC4888856 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other

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Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.

Lückoff Anika A   Caramoy Albert A   Scholz Rebecca R   Prinz Marco M   Kalinke Ulrich U   Langmann Thomas T  

EMBO molecular medicine 20160601 6


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 I  ...[more]

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