title: IL-27 inhibits pathophysiological intraocular neovascularization due to laser burn.
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.
authors: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Eiichi
authors: E
authors: Hasegawa
authors: Yuji
authors: Y
authors: Oshima
authors: Atsunobu
authors: A
authors: Takeda
authors: Kazuko
authors: K
authors: Saeki
authors: Hiroki
authors: H
authors: Yoshida
authors: Koh-Hei
authors: KH
authors: Sonoda
authors: Tatsuro
authors: T
authors: Ishibashi
mesh_terms: D000818:Animals; D002829:Choroid / Q000293:injuries*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000517:prevention & control*; D005126:Eye Burns / Q000150:complications*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D017075:Laser Coagulation / Q000009:adverse effects*; D007834:Lasers / Q000009:adverse effects*; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000172:deficiency / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: C499601:Ebi3 protein, mouse; C556062:IL10 protein, mouse; C486767:Il27 protein, mouse; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016753:Interleukin-10