title: The inhibitory effects of bevacizumab eye drops on NGF expression and corneal wound healing in rats.
abstract: OBJECTIVE
  To investigate the effect of bevacizumab eye drops on corneal epithelial wound healing in rats.
  
  
  METHODS
  One hundred twenty Sprague-Dawley male rat corneas were divided into two groups and de-epithelized with a microblade. The bevacizumab group was treated with 5% bevacizumab and antibiotic 0.5% levofloxacin eye drops four times daily and the control group with antibiotic eye drops only. Corneal wound healing was evaluated by fluorescein staining at initial wounding and 24, 48, and 72 hours after epithelial debridement. Nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) proteins were measured in rat corneas by ELISA. Immunofluorescent staining for NGF and VEGF was performed in rat corneas. NGF mRNA and VEGF mRNA was measured in rat corneas by real-time PCR.
  
  
  RESULTS
  The corneal wound healing rate was decreased in the bevacizumab group compared with that in the control group. Twenty-four, 48, and 72 hours after epithelial debridement, corneal NGF and VEGF proteins in the bevacizumab group were lower than that in the control group (P<0.05). Immunofluorescent staining showed that NGF and VEGF expression was stronger in the control group than in the bevacizumab group. NGF mRNA and VEGF mRNA levels in the bevacizumab group were also lower than in the control group (P<0.05).
  
  
  CONCLUSIONS
  After corneal epithelial damage, VEGF and NGF increased normally in the rat corneas. In contrast, when VEGF was inhibited by bevacizumab eye drops, the wound healing rate was decreased, and NGF was downregulated. Bevacizumab eye drops have an inhibitory effect on corneal wound healing in rats.
authors.affiliation: Department of Ophthalmology and Visual Science, Institute of Clinical Medicine Research, College of Medicine, Catholic University of Korea, and Department of Ophthalmology, Seoul St. Mary's Hospital, Seoul, Korea.
authors.forename: Eun Chul
authors.initials: EC
authors.lastname: Kim
authors.forename: Weon Sun
authors.initials: WS
authors.lastname: Lee
authors.forename: Man Soo
authors.initials: MS
authors.lastname: Kim
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003315:Cornea / Q000187:drug effects / Q000502:physiology; D065306:Corneal Injuries; D003646:Debridement; D019793:Fluorescein; D005455:Fluorescent Antibody Technique; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009883:Ophthalmic Solutions; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000068258:Bevacizumab; D020932:Nerve Growth Factor; D019793:Fluorescein