Intravitreal conbercept improves outcome of proliferative diabetic retinopathy through inhibiting inflammation and oxidative stress

Abstract

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.