Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.
Anika LückoffAlbert CaramoyRebecca ScholzMarco PrinzUlrich KalinkeThomas LangmannPublished in: EMBO molecular medicine (2016)
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.
Keyphrases
- age related macular degeneration
- diabetic retinopathy
- dendritic cells
- wild type
- immune response
- early stage
- optical coherence tomography
- optic nerve
- peripheral blood
- vascular endothelial growth factor
- adipose tissue
- inflammatory response
- neuropathic pain
- high speed
- endothelial cells
- patient safety
- breast cancer cells
- gene expression
- estrogen receptor
- stem cells
- squamous cell carcinoma
- human health
- type diabetes
- bone marrow
- single cell
- newly diagnosed
- dna methylation
- quality improvement
- sentinel lymph node
- insulin resistance