Difference in the Vitreal Protein Profiles of Patients with Proliferative Diabetic Retinopathy with and without Intravitreal Conbercept Injection.

Chen Zou,Xinping She,Minjie Zhao,Zhi Zheng,Dandan Zhu,Yanan Hu,Jingjing Yu,Yunzhi Wang

doi:10.1155/2018/7397610

Abstract

Purpose To examine the difference in the vitreal protein profiles of patients with proliferative diabetic retinopathy (PDR) with and without preoperative intravitreal conbercept (IVC) treatment. Methods Liquid chromatography-tandem mass spectrometry- (LC-MS/MS-) based proteomic methods were used to determine the protein profiles of the vitreous humor in patients with PDR treated with (IVC group; n = 9) and without (PDR group; n = 8) preoperative IVC. Gene ontology (GO) annotation and REACTOME pathway analysis were obtained to overview differentially expressed proteins between each group. Intravitreal levels of apolipoprotein A-II (APOA2) and ceruloplasmin (CP) were measured using enzyme-linked immunosorbent assays. Results 307 proteins were expressed differentially between PDR and IVC groups, including 218 proteins downregulated in response to IVC. The most notable GO annotations in level 3 and REACTOME pathways describing the differentially expressed proteins were “innate immune response” and “platelet degranulation.” The intravitreal levels of APOA2 and CP were lower in the IVC group than in the PDR group (p < 0.01). Conclusions In addition to decreasing the intravitreal vascular endothelial growth factor level, IVC may alter the vitreal protein profile in patients with PDR, with the differentially regulated proteins involved in the immune response, platelet degranulation, complement activation, and inflammation.

Highlights

Vascular endothelial growth factor (VEGF) is the major mediator of intraocular neovascularization and abnormal vessel permeability and plays a pivotal role in the pathogenesis of diabetic retinopathy [1, 2]
Conbercept (Kanghong Biotechnologies) is a recombinant fusion protein composed of the second immunoglobulin (Ig) domain of vascular endothelial growth factor receptor-1 (VEGFR1) and the third and fourth Ig domains of vascular endothelial growth factor receptor-2 (VEGFR2), fused to the constant region (Fc) of human IgG1, and it acts as a receptor with affinity for all informs of VEGF and placental growth factor (PlGF) [5,6,7]
Among the 450 proteins identified in both groups, 3 proteins were significantly upregulated and 14 proteins were significantly downregulated in the intravitreal conbercept (IVC) group compared with the proliferative diabetic retinopathy (PDR) group (p < 0 05; Supplementary Table S3)

Summary

Introduction

Vascular endothelial growth factor (VEGF) is the major mediator of intraocular neovascularization and abnormal vessel permeability and plays a pivotal role in the pathogenesis of diabetic retinopathy [1, 2]. Several drugs that act against VEGF have been developed; these drugs include bevacizumab (Avastin; Novartis), a recombinant humanized monoclonal antibody, and ranibizumab (Lucentis; Novartis), a Fab fragment that is similar to bevacizumab. Conbercept (Kanghong Biotechnologies) is a recombinant fusion protein composed of the second immunoglobulin (Ig) domain of vascular endothelial growth factor receptor-1 (VEGFR1) and the third and fourth Ig domains of vascular endothelial growth factor receptor-2 (VEGFR2), fused to the constant region (Fc) of human IgG1, and it acts as a receptor with affinity for all informs of VEGF and placental growth factor (PlGF) [5,6,7]. Intravitreal injection of aflibercept is used widely in the treatment of proliferative diabetic retinopathy (PDR).

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Conclusion