Zhang Yuanyuan, Zhu Shaopin, Xu Xun, Zuo Lei
Department of Ophthalmology, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai 200081, China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
J Ophthalmol. 2019 Oct 27;2019:7419571. doi: 10.1155/2019/7419571. eCollection 2019.
This is an in vitro study conducted to observe the safety and antiscarring effects of combined application of bevacizumab (BVZ) and 5-fluorouracil (5-Fu) or BVZ and mitomycin C (MMC) during glaucoma filtration surgery (GFS). The cytotoxicity of drug combinations in human Tenon's fibroblasts (HTFs) and human umbilical vein endothelial cells (HUVECs) was evaluated. Their effects on the levels of vascular endothelial growth factor (VEGF) in HUVECs, cell proliferation and migration in HTFs, and the expression of collagen type I alpha 1 (Col1A1) gene in HTFs were evaluated. In addition, the effects of combined drugs on VEGF(R) mRNA in HTFs were detected to explore the possible underlying drug mechanisms. The results showed that BVZ combined with 5-Fu demonstrated more significant antiscarring effects than BVZ or 5-Fu alone. However, the inhibitory effects of BVZ combined with MMC were similar to those of MMC alone. The cytotoxicity of the drug combinations was significantly greater than that of single drug, suggesting that combined application of BVZ and antimetabolites after GFS was safer when applied at different sites (such as subconjunctival injection at bilateral sides of the filtering bleb) or at varied time points.
这是一项体外研究，旨在观察在青光眼滤过手术（GFS）期间联合应用贝伐单抗（BVZ）与5-氟尿嘧啶（5-Fu）或BVZ与丝裂霉素C（MMC）的安全性和抗瘢痕形成作用。评估了药物组合对人Tenon囊成纤维细胞（HTFs）和人脐静脉内皮细胞（HUVECs）的细胞毒性。评估了它们对HUVECs中血管内皮生长因子（VEGF）水平、HTFs中细胞增殖和迁移以及HTFs中I型胶原蛋白α1（Col1A1）基因表达的影响。此外，检测了联合用药对HTFs中VEGF（R）mRNA的影响，以探讨可能的潜在药物作用机制。结果表明，BVZ与5-Fu联合应用比单独使用BVZ或5-Fu具有更显著的抗瘢痕形成作用。然而，BVZ与MMC联合应用的抑制作用与单独使用MMC相似。药物组合的细胞毒性明显大于单一药物，这表明在GFS后，当在不同部位（如滤过泡两侧结膜下注射）或不同时间点应用时，联合应用BVZ和抗代谢药物更安全。
