CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases

Blood vessel dysfunction causes several retinal diseases,including diabetic retinopathy,familial exudative vitreoretinopathy,macular degeneration and choroidal neovascularization in pathological myopia.Vascular endothelial growth factor(VEGF)-neutralizing proteins provide benefits in most of those diseases,yet unsolved haemorrhage and frequent intraocular injections still bothered patients.Here,we identified endothelial CD146 as a new target for retinal diseases.CD146 expression was activated in two ocular pathological angiogenesis models,a laser-induced choroid neovascularization model and an oxygeninduced retinopathy model.The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model.Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models.Mechanistically,under hypoxia condition,CD146 was involved in the activation of NFκB,Erk and Akt signalling pathways,which are partially independent of VEGF.Consistently,anti-CD146therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo.Given the critical role of abnormal angiogenesis in retinal and choroidal diseases,our results provide novel insights into combinatorial therapy for neovascular fundus diseases.