Abstract
AMD is the most common disease leading to acquired blindness in developed countries. CNV is the foremost cause of AMD and is thought to be induced by regional inflammation as a result of age-related conformational changes of the chorioretinal interface. Here, we show that IL-27, a member of the IL-6/IL-12 cytokine family, has an angiostatic effect and regulates the development of laser-induced experimental CNV in mice. In this model, IL-27 expression increased in the damaged choroid and peaked at the 24 h-time-point. IL-27 neutralization, induced by inoculating an antagonistic antibody into the vitreous cavity, enhanced VEGF production and the extent of CNV. By contrast, the administration of rIL-27 reduced VEGF production and the extent of CNV. Mice deficient in the EBI3, which lack IL-27, also showed more CNV than C57BL/6 mice, and this was reduced by IL-27 supplementation. We additionally investigated the effect of IL-27 on the function of macrophages, which play a critical role in CNV. IL-27 did not affect macrophage migration but inhibited its VEGF production. IL-27 therefore appears to regulate CNV and is a promising candidate target for treating sight-threatening diseases caused by ocular neovascularization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Choroid / injuries*
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Choroidal Neovascularization / etiology
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Choroidal Neovascularization / prevention & control*
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Eye Burns / complications*
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Interleukin-10 / biosynthesis
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Interleukin-10 / genetics
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Interleukins / biosynthesis
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Interleukins / genetics
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Interleukins / physiology
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Interleukins / therapeutic use*
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Laser Coagulation / adverse effects*
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Lasers / adverse effects*
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Macrophage Activation / drug effects
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Minor Histocompatibility Antigens
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Receptors, Cytokine / deficiency
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Receptors, Cytokine / physiology
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Recombinant Fusion Proteins / therapeutic use
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STAT1 Transcription Factor / metabolism
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STAT3 Transcription Factor / metabolism
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Specific Pathogen-Free Organisms
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Up-Regulation
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Vascular Endothelial Growth Factor A / biosynthesis
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Vascular Endothelial Growth Factor A / genetics
Substances
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Ebi3 protein, mouse
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IL10 protein, mouse
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Il27 protein, mouse
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Interleukins
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Minor Histocompatibility Antigens
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RNA, Messenger
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Receptors, Cytokine
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Recombinant Fusion Proteins
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STAT1 Transcription Factor
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STAT3 Transcription Factor
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Stat1 protein, mouse
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Stat3 protein, mouse
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Vascular Endothelial Growth Factor A
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vascular endothelial growth factor A, mouse
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Interleukin-10