Kang Seungbum, Choi Hyunsu, Rho Chang Rae
1 Department of Ophthalmology and Visual Science, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
2 Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea , Daejeon, Republic of Korea.
J Ocul Pharmacol Ther. 2016 Dec;32(10):671-676. doi: 10.1089/jop.2016.0094. Epub 2016 Nov 9.
This study compared the effects of 3 antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) on corneal epithelial cell viability and wound healing using human corneal epithelial cells (HCECs).
To determine the cytotoxic effects of anti-VEGF agents on HCECs, HCEC viability was determined at various concentrations of these agents. An in vitro migration assay was used to investigate the migration of HCECs treated with 3 anti-VEGF agents. The protein level of extracellular signal-regulated kinase was used to evaluate the effect of anti-VEGF treatment on cell proliferation. The protein levels of p38 mitogen-activated protein kinase (MAPK) were analyzed by Western blotting to investigate cell migration.
After 24 or 48 h of exposure, aflibercept treatment showed no apparent effect on cell viability; however, bevacizumab and ranibizumab treatment decreased cell viability at high concentrations (1 and 2 mg/mL). A migration assay showed that HCEC migration was different among the 3 anti-VEGF treatment groups. Bevacizumab significantly delayed HCEC migration. Western blotting showed that bevacizumab treatment decreased the expression levels of phosphorylated p38 MAPK.
Bevacizumab, the most widely used and investigated anti-VEGF agent, decreased epithelial cell migration and viability. Anti-VEGF agents other than bevacizumab might therefore be better for treating corneal neovascularization complicated with epithelial defects.
本研究使用人角膜上皮细胞（HCECs）比较了3种抗血管内皮生长因子（VEGF）药物（贝伐单抗、雷珠单抗和阿柏西普）对角膜上皮细胞活力及伤口愈合的影响。
为确定抗VEGF药物对HCECs的细胞毒性作用，在这些药物的不同浓度下测定HCEC活力。采用体外迁移试验研究经3种抗VEGF药物处理的HCECs的迁移情况。利用细胞外信号调节激酶的蛋白水平评估抗VEGF治疗对细胞增殖的影响。通过蛋白质印迹法分析p38丝裂原活化蛋白激酶（MAPK）的蛋白水平以研究细胞迁移。
暴露24或48小时后，阿柏西普处理对细胞活力无明显影响；然而，高浓度（1和2mg/mL）的贝伐单抗和雷珠单抗处理会降低细胞活力。迁移试验表明，3个抗VEGF治疗组的HCEC迁移情况不同。贝伐单抗显著延迟了HCEC迁移。蛋白质印迹法显示，贝伐单抗处理降低了磷酸化p38 MAPK的表达水平。
使用最广泛且研究最多的抗VEGF药物贝伐单抗降低了上皮细胞迁移和活力。因此，除贝伐单抗外的抗VEGF药物可能更适合治疗合并上皮缺损的角膜新生血管。
