title: Bevacizumab eye drops delay corneal epithelial wound healing and increase the stromal response to epithelial injury in rats.
abstract: BACKGROUND
  To evaluate the effects of bevacizumab eye drops on corneal epithelial wound healing and the stromal response after epithelial injury in rats.
  
  
  METHODS
  We divided 160 Sprague-Dawley male rats into two groups and de-epithelized corneas with a microblade. Five percent bevacizumab (Avastin) and antibiotic (Cravit) eyedrops were treated four times daily in the bevacizumab group and antibiotic eye drops only in the control group. Wound area evaluation, enzyme-linked immunosorbent assay, immunofluorescent staining, and real-time polymerase chain reaction were performed with rat corneas.
  
  
  RESULTS
  The percentage of wound healing in the bevacizumab group was lower than in the control group at 24, 48 and 72 hours after epithelial debridement (P = 0.02, 0.01 and 0.01). Corneal matrix metalloproteinase-2 (P = 0.02, 0.01 and 0.02), matrix metalloproteinase-9 (P = 0.03, 0.01 and 0.01) and transforming growth factor-β (P = 0.02, 0.02 and 0.01) proteins in the bevacizumab group were higher than control group at 24, 48, and 72 hours. Matrix metalloproteinase-2, matrix metalloproteinase-9, transforming growth factor-b and a-smooth muscle actin were strongly stained in the bevacizumab corneas compared with control corneas in immunofluorescent staining. Matrix metalloproteinase-2 (P = 0.04, 0.03 and 0.04), matrix metalloproteinase- 9 (P = 0.03, 0.01 and 0.02), transforming growth factor-b (P = 0.03, 0.03 and 0.03) and a-smooth muscle actin (P = 0.04, 0.01 and 0.04) messenger RNA levels in the bevacizumab group were also highly expressed compared with the control group at 24, 48, and 72 hours.
  
  
  CONCLUSIONS
  The bevacizumab eye drops delay the wound healing and increase stromal response after corneal epithelial injury in rats.
authors: Department of Ophthalmology and Visual Science, Catholic University of Korea, Seoul, Korea.
authors: Eun Chul
authors: EC
authors: Kim
authors: Hyun Wook
authors: HW
authors: Ryu
authors: Hee Jin
authors: HJ
authors: Lee
authors: Man Soo
authors: MS
authors: Kim
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D003319:Corneal Stroma / Q000187:drug effects* / Q000378:metabolism; D003646:Debridement; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000293:injuries* / Q000378:metabolism; D005131:Eye Injuries / Q000188:drug therapy* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009883:Ophthalmic Solutions; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014945:Wound Healing / Q000187:drug effects*; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000199:Actins; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C498862:Acta2 protein, rat; C467498:vascular endothelial growth factor A, rat; C522363:Mmp2 protein, rat; C572337:Mmp9 protein, rat
keywords: MMP; bevacizumab eye drop; corneal wound healing; myofibroblast transformation; stromal response