Proteomic analysis of anti-angiogenic effects by conbercept in the mice with oxygen induced retinopathy

Ji Jin; Lei Chen; Gao-Qin Liu; Pei-Rong Lu

doi:10.18240/ijo.2020.12.02

Proteomic analysis of anti-angiogenic effects by conbercept in the mice with oxygen induced retinopathy

Int J Ophthalmol. 2020 Dec 18;13(12):1844-1853. doi: 10.18240/ijo.2020.12.02. eCollection 2020.

Authors

Ji Jin^{1

2}, Lei Chen³, Gao-Qin Liu¹, Pei-Rong Lu¹

Affiliations

¹ Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
² Department of Ophthalmology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
³ Department of Ophthalmology, Children's Hospital of Soochow University, Suzhou 215025, Jiangsu Province, China.

Abstract

Aim: To analyze the retinal proteomes with and without conbercept treatments in mice with oxygen-induced retinopathy (OIR) and identify proteins involved in the molecular mechanisms mediated by conbercept.

Methods: OIR was induced in fifty-six C57BL/6J mouse pups and randomly divided into four groups. Group 1: Normal17 (n=7), mice without OIR and treated with normal air. Group 2: OIR12/EXP1 (n=14), mice received 75% oxygen from postnatal day (P) 7 to 12. Group 3: OIR17/Control (n=14), mice received 75% oxygen from P7 to P12 and then normal air to P17. Group 4: Lang17/EXP2 (n=21), mice received 75% oxygen from P7 to P12 with intravitreal injection of 1 µL conbercept at the concentration of 10 mg/mL at P12, and then normal air from P12 to P17. Liquid Chromatography-Mass Spectrometry (LC-MS)/MS data were reviewed to find proteins that were up-regulated after the conbercept treatment. Gene ontology (GO) analysis was performed of conbercept-mediated changes in proteins involved in single-organism processes, biological regulation, cellular processes, immune responses, metabolic processes, locomotion and multiple-organism processes.

Results: Conbercept induced a reversal of hypoxia-inducible factor 1 signaling pathway as revealed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and also induced down-regulation of proteins involved in blood coagulation and fibrin clot formation as demonstrated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) and the stimulation of interferon genes studies. These appear to be risk factors of retinal fibrosis. Additional conbercept-specific fibrosis risk factors were also identified and may serve as therapeutic targets for fibrosis.

Conclusion: Our studies reveal that many novel proteins are differentially regulated by conbercept. The new insights may warrant a valuable resource for conbercept treatment.

Keywords: anti-vascular endothelial growth factor; conbercept; fibrosis; proteomic analysis; retinopathy.

International Journal of Ophthalmology Press.