Effect And Mechanism Of IL-23 On Ocular Neovascularization

Objective: To investigate the possible role and mechanism of IL-23 in the processing of ocular neovascularization(NV).Methods: In vivo study,oxygen-induced retinopathy(OIR)model was used to detect the IL-23 expression at specific time points.The anti-angiogenic activity of IL-23 neutralizing antibody(NAb)was investigated by intravitreous administration in mice OIR model and choroidal neovascularization(CNV)model induced by laser photocoagulation to rupture Bruch's membrane.Immunofluorescent staining was applied to observe the location and relationship between IL-23 and endothelial cells,macrophages,et al.The expressions of several angiogenic factors were investigated after IL-23 neutraliztion.The effect of IL-23 on human retinal endothelial cells(HRECs)tube formation and macrophages migration were investigated in vitro.Results: Significantly higher expression of IL-23 in the retinas with OIR was observed,and might mainly be secreted by the müller cells and infiltrated macrophages.After neutralizing IL-23,the expressions of the angiogenic factors including vascular endothelial growth factor(VEGF)and its receptors(VEGFR1 and VEGFR2),placental growth factor(PLGF),angiopoietin 2(ang2)and endothelial-specific receptor tyrosine kinase(Tie2),inducible nitric-oxide synthase(iNOS)and matrix metalloproteinase(MMP)s were significantly down regulated,while the anti-angiogenic molecules including chemokine(C-X-C motif)ligand(CXCL)9 and CXCL10 were significantly up regulated.IL-23 blockade caused less NV in both the RNV and CNV mouse models.In addition,the in vitro assay showed that IL-23 alone is able to stimulate the ability of endothelial cells to form tubes and migration of macrophages.Conclusions: IL-23 has pro-angiogenic effect on ocular NV and could be a potential therapeutic target for RNV and CNV diseases.