Li Hou-Shuo, Lyu Xiao, Rong Ao, Bi Yan-Long, Xu Wei, Cui Hong-Ping
Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Department of Ophthalmology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Int J Ophthalmol. 2024 Oct 18;17(10):1816-1827. doi: 10.18240/ijo.2024.10.07. eCollection 2024.
To investigate the role of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy (PDR) following intravitreal injection of conbercept.
This study included 72 PDR patients and 8 cataract patients as controls. PDR patients were divided into 3 groups according to the intervals of 3, 5, and 7d between intravitreal conbercept (IVC, 0.5 mg/0.05 mL) injection and pars plana vitrectomy (PPV) performed. Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay (ELISA). The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the data, and the protein interaction network of 23 differential proteins was studied.
Post-IVC, VEGF levels decreased and CTGF levels increased significantly in aqueous humor, with the CTGF/VEGF ratio rising significantly at all intervals. Liquid chromatography tandem mass spectrometry (LC-MS/MS) identified differentially expressed proteins between pre- and post-IVC samples. GO and KEGG analyses revealed involvement in immune response, stress response, complement and coagulation cascades, ferroptosis, and PPAR signaling pathways. PPI analysis highlighted key proteins like APOA1, C3, and transferrin (TF). ELISA assay confirmed the differential expression of proteins such as HBA1, SERPINA1, COL1A1, and ACTB, with significant changes in the IVC groups.
The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels, thereby modifying the CTGF/VEGF ratio, and IVC significantly alters the protein profile in the aqueous humor of patients with PDR. Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response, stress response, and cellular metabolism.
探讨结缔组织生长因子（CTGF）和血管内皮生长因子（VEGF）在玻璃体内注射康柏西普后增殖性糖尿病视网膜病变（PDR）患者房水蛋白质谱中的作用。
本研究纳入72例PDR患者和8例白内障患者作为对照。PDR患者根据玻璃体内注射康柏西普（IVC，0.5mg/0.05mL）与进行玻璃体切割术（PPV）之间3、5和7天的间隔分为3组。在IVC和PPV前后采集房水样本，用酶联免疫吸附测定（ELISA）检测VEGF和CTGF水平。对IVC后5天接受PPV手术的10例患者和8例正常对照进行差异蛋白质组学研究，对数据进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，并研究23种差异蛋白质的蛋白质相互作用网络。
IVC后，房水中VEGF水平降低，CTGF水平显著升高，所有间隔的CTGF/VEGF比值均显著升高。液相色谱串联质谱（LC-MS/MS）鉴定了IVC前后样本之间的差异表达蛋白质。GO和KEGG分析显示参与免疫反应、应激反应、补体和凝血级联、铁死亡和PPAR信号通路。蛋白质-蛋白质相互作用（PPI）分析突出了载脂蛋白A1（APOA1）、补体C3（C3）和转铁蛋白（TF）等关键蛋白质。ELISA测定证实了血红蛋白A1（HBA1）、丝氨酸蛋白酶抑制剂A1（SERPINA1）、Ⅰ型胶原蛋白α1链（COL1A1）和肌动蛋白β（ACTB）等蛋白质的差异表达，IVC组有显著变化。
该研究表明，IVC有效降低VEGF水平，同时升高CTGF水平，从而改变CTGF/VEGF比值，IVC显著改变PDR患者房水的蛋白质谱。蛋白质组学分析表明，这些变化与免疫反应、应激反应和细胞代谢中涉及的关键生物学途径和蛋白质相互作用有关。
