Differential Effects of Bevacizumab, Ranibizumab, and Aflibercept on the Viability and Wound Healing of Corneal Epithelial Cells.
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.
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.
Seungbum
S
Kang
2 Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea , Daejeon, Republic of Korea.
Hyunsu
H
Choi
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.
Chang Rae
CR
Rho
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000068258:Bevacizumab / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D019573:Epithelium, Corneal / Q000187:drug effects; D006801:Humans; D000069579:Ranibizumab / Q000494:pharmacology*; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors; D014945:Wound Healing / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D042442:Vascular Endothelial Growth Factors; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
MAP kinase; VEGF; corneal epithelium; signal transduction