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

• Published in: Life sciences (1973) Vol. 265; p. 118795
• Main Authors: Xia, Jian-Ping, Liu, Sheng-Qiang, Wang, Shuai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.01.2021; Elsevier BV
• Subjects: Aged; Aged, 80 and over; Angiogenesis; Angiography; Animals; Cell adhesion; Cell adhesion molecules; Cell proliferation; Conbercept; Diabetes; Diabetes mellitus; Diabetic retinopathy; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; drugs; Endothelial cells; Female; fluorescent antibody technique; Glutathione; Growth factors; histology; Humans; Immunofluorescence; Inflammation; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Intercellular adhesion molecule 1; Interleukin 6; Intravitreal Injections - methods; Macrophage inflammatory protein; Macrophage inflammatory protein 1; macrophage inflammatory proteins; Male; Mice; Mice, Inbred C57BL; Microvasculature; Middle Aged; Molecular modelling; Morphology; mRNA; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Polymerase chain reaction; Proliferative diabetic retinopathy; Prostaglandin E1; Prostaglandin E2; Prostaglandins; Proteins; quantitative polymerase chain reaction; Recombinant Fusion Proteins - administration & dosage; Retina; Retinopathy; ROS; Streptozocin; streptozotocin; tomography; Treatment Outcome; Vascular endothelial growth factor; Oxidative stress; Inflammation; Conbercept; Proliferative diabetic retinopathy; ROS
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2020.118795

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. [Display omitted] •Inflammation and oxidative stress increased in aqueous fluid of human with PDR.•Conbercept alleviated VEGF-downstream inflammation response.•Conbercept inhibited oxidative stress in retina of PDR mice.