Intravitreal Conbercept As An Adjunct To Vitrectomy For Proliferative Diabetic Retinopathy Induced Changes In Vitreous Protein Expression Profile

Objective:To observe the efficacy of preoperative anti-vascular endothelial growth factors(anti-VEGF)therapy on proliferative diabetic retinopathy(PDR)patients.To investigate the change of protein profile induced by conbercept in vitreous humor and explore the effects and underlying mechanism of anti-VEGF treatment on PDR.Methods:This is a controlled clinical trail.A total 40 patients(40 eyes)with the diagnosis of PDR Tianjin Medical University Eye Hospital from January 2018 to December 2018 were randomly selected and included in the study.They were divided into two groups: 20 patients who received intravitreal injection of conbercept before vitrectomy(IVC group)and 20 patients who only received vitrectomy(PDR group).The best corrected visual acuity(BCVA)and operation complexity were recorded.In this study,36 vitreous humor samples were collected,an immunodepletion kit was used for optimal removal of the high-abundance vitreous proteins.The potential changes induced by VEGF inhibitors were analyzed using Tandem Mass Tag(TMT)-based quantitative proteomic strategy.Enzyme-linked immunology sorbent assays(ELISA)were employed to confirm concentration of the selected proteins and validate the proteomic results.Result:1、40 eyes of 40 cases were enrolled and 36 patients were followed up.There was no significant difference in gender,glycosylated hemoglobin level,duration of diabetes and preoperative BCVA(Log MAR)between the two groups(P > 0.05).2、Preoperative anti-VEGF therapy regressed neovascularization,shortened the surgical time(P = 0.027)and reduced the chance of intraoperative bleeding(P = 0.026),whereas aggravated retinal fibrosis.There was no significant difference in silicone oil tamponade rate(P > 0.05).BCVA in IVC group was significantly better than that in PDR group(P < 0.05).3、No serious complications occurred in both groups during the follow-up period.4、After effectively removing high abundance protein from vitreous body fluid,we subsequently quantified 853 vitreous proteins by proteomics.Differentially expressed proteins were found in the extracellular and intracellular regions and were involved in VEGF binding and VEGF-activated receptor activity.Protein–protein interactions indicated associations with fibrosis,neovascularization,and inflammatory signaling pathways.5、Protein-protein interaction analysis showed that the differentially expressed proteins were involved in the signaling pathways of fibrosis,neovascularization and inflammation.Conclusion:1、Preoperative anti-VEGF therapy can effectively assist vitrectomy and reduce the complexity of vitrectomy.Patients of IVC group can get better visual prognosis.2、In addition to VEGF,conbercept can affect the levels of various proteins in the vitreous of PDR patients.The differential expression of proteins involved in the signal pathways of fibrosis,neovascularization and inflammation,suggesting that IVC involved in the related signal pathways.Multiple signal pathways are the mechanism of conbercept in the treatment of PDR,and also the key to the aggravation of preretinal proliferative membrane.3、High abundance protein removal combined with TMT-labeled quantitative proteomics provides a platform for screening low abundance differentially expressed proteins with biological significance,and lays a foundation for exploring new targets of PDR treatment.