| First Author | Lückoff A | Year | 2016 |
| Journal | EMBO Mol Med | Volume | 8 |
| Issue | 6 | Pages | 670-8 |
| PubMed ID | 27137488 | Mgi Jnum | J:294812 |
| Mgi Id | MGI:6451367 | Doi | 10.15252/emmm.201505994 |
| Citation | Luckoff A, et al. (2016) Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization. EMBO Mol Med 8(6):670-8 |
| abstractText | 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-beta signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD Complete deletion of interferon-alpha/beta 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-beta 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-beta therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. |
