Open AccessInterferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization
Author(s) -
Lückoff Anika,
Caramoy Albert,
Scholz Rebecca,
Prinz Marco,
Kalinke Ulrich,
Langmann Thomas
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201505994
Subject(s) - retinal , neovascularization , immunology , interferon , interferon beta , pathological , signal transduction , medicine , cancer research , microbiology and biotechnology , biology , pathology , angiogenesis , ophthalmology
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 Ifnar 1 −/− 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 .