Conbercept is a newly-developed anti-vascular endothelial growth factor (VEGF) drug. This study aimed to evaluate the effects of conbercept on inflammation and oxidative response in proliferative diabetic retinopathy (PDR). Morphology changes in retinal microvasculature of PDR patients were determined by optical coherence tomographic angiography (OCTA). The mice were injected with streptozocin (STZ) for 20 weeks to induced PDR, then the changes in inflammatory factors, oxidative response and histological analysis were examined with Elisa assay, real time-PCR and commercial kits analysis. Conbercept treatment significantly alleviated the retinal pathological changes and significantly reduced intercellular cell adhesion molecule-1 (ICAM-1), macrophage inflammatory protein-1 (MIP-1), IL-1β, IL-6 and TNF-α protein levels but not prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) levels, all of which were remarkably elevated in aqueous fluid of PDR patients compared with non-PDR subjects. Meanwhile the inhibitory effects of conbercept on these inflammatory factors were proved by RT-PCR assays in mice experiments. And the inflammatory signal such as p-IKBα and p-p65 was correspondingly inhibited by conbercept in STZ-treated mice. Conbercept treatment significantly elevated the aqueous glutathione level of PDR patients and inhibited NOX-1, NOX-4 and ph22phox mRNA expressions and ROS production of PDR mice. Ki67 immunofluorescence staining showed that conbercept inhibited endothelial cell proliferation in retina of PDR mice. In conclusion, conbercept significantly inhibited the angiogenesis, inflammation and oxidative response in PDR mice, and these findings further reveals the molecular mechanisms of conbercept in treating PDR.

Conbercept是一种新开发的抗血管内皮生长因子（VEGF）药物。这项研究旨在评估conbercept对增生性糖尿病视网膜病变（PDR）中炎症和氧化反应的影响。通过光学相干断层扫描血管造影（OCTA）确定PDR患者的视网膜微血管形态学变化。给小鼠注射链脲佐菌素（STZ）20周以诱导PDR，然后通过Elisa测定，实时PCR和商业试剂盒分析检查炎症因子，氧化反应和组织学分析的变化。Conbercept治疗可显着缓解视网膜病理变化，并显着降低细胞间细胞粘附分子1（ICAM-1），巨噬细胞炎性蛋白1（MIP-1），IL-1β，IL-6和TNF-α蛋白水平升高，但前列腺素E1（PGE1），前列腺素E2（PGE2）和前列腺素F2a（PGF2a）水平却没有升高，与非PDR患者相比，PDR患者的水液中所有这些均显着升高。同时通过小鼠实验中的RT-PCR分析证实了conbercept对这些炎症因子的抑制作用。在conzcept中，STZ处理的小鼠相应地抑制了p-IKBα和p-p65等炎症信号。Conbercept治疗可显着提高PDR病人的谷胱甘肽水平，并抑制PDR小鼠的NOX-1，NOX-4和ph22phox mRNA表达以及ROS的产生。Ki67免疫荧光染色表明，conbercept抑制了PDR小鼠视网膜中的内皮细胞增殖。总之，conbercept显着抑制了血管生成，