Jin Ji, Chen Lei, Liu Gao-Qin, Lu Pei-Rong
Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
Department of Ophthalmology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
Int J Ophthalmol. 2020 Dec 18;13(12):1844-1853. doi: 10.18240/ijo.2020.12.02. eCollection 2020.
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.
OIR was induced in fifty-six C57BL/6J mouse pups and randomly divided into four groups. Group 1: Normal17 (=7), mice without OIR and treated with normal air. Group 2: OIR12/EXP1 (=14), mice received 75% oxygen from postnatal day (P) 7 to 12. Group 3: OIR17/Control (=14), mice received 75% oxygen from P7 to P12 and then normal air to P17. Group 4: Lang17/EXP2 (=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.
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.
Our studies reveal that many novel proteins are differentially regulated by conbercept. The new insights may warrant a valuable resource for conbercept treatment.
分析氧诱导性视网膜病变（OIR）小鼠在接受和未接受康柏西普治疗时的视网膜蛋白质组，并鉴定参与康柏西普介导的分子机制的蛋白质。
56只C57BL/6J幼鼠诱导产生OIR，并随机分为四组。第1组：正常17只（=7只），未患OIR且用正常空气处理的小鼠。第2组：OIR12/EXP1（=14只），从出生后第（P）7天至12天接受75%氧气的小鼠。第3组：OIR17/对照（=14只），从P7至P12接受75%氧气，然后至P17接受正常空气的小鼠。第4组：Lang17/EXP2（=21只），从P7至P12接受75%氧气，在P12时玻璃体腔内注射1 μL浓度为10 mg/mL的康柏西普，然后从P12至P17接受正常空气的小鼠。对液相色谱-质谱联用（LC-MS）/MS数据进行审查，以寻找康柏西普治疗后上调的蛋白质。对参与单细胞过程、生物调节、细胞过程、免疫反应、代谢过程、运动和多细胞过程的蛋白质中康柏西普介导的变化进行基因本体（GO）分析。
京都基因与基因组百科全书（KEGG）分析显示，康柏西普诱导缺氧诱导因子1信号通路逆转，注释、可视化和综合发现数据库（DAVID）及干扰素基因刺激研究表明，康柏西普还诱导参与血液凝固和纤维蛋白凝块形成的蛋白质下调。这些似乎是视网膜纤维化的危险因素。还鉴定出了其他康柏西普特异性纤维化危险因素，可作为纤维化的治疗靶点。
我们的研究表明，许多新蛋白质受康柏西普的差异调节。这些新见解可能为康柏西普治疗提供宝贵资源。
