title: Effect of intravitreal injection of bevacizumab on optic nerve head leakage and retinal ganglion cell survival in a mouse model of optic nerve crush.
abstract: OBJECTIVE
  To evaluate the effect of bevacizumab, a VEGF inhibitor, on optic nerve edema and retinal ganglion cell (RGC) loss in a mouse model of optic nerve crush (ONC).
  
  
  METHODS
  Two hundred C57BL/6 wild-type mice were anesthetized. Right ONC was induced in 150 mice, of which half (n = 75) received an intravitreal injection of bevacizumab immediately thereafter and half (n = 75) did not. The remaining 50 received only bevacizumab. The left eyes served as a control. Findings were analyzed by fluorescein angiography (days 0, 1, 3), histologic and immunohistochemical tests (days 1, 3, 4, 21), and quantitative real-time PCR.
  
  
  RESULTS
  Angiography revealed a reduction in postinjury disc leakage following bevacizumab injection (days 1, 3), confirmed with IgG staining. On PCR, expression of HO-1 and SOD-1 mRNA increased following ONC and further increased with bevacizumab. VEGF gene expression decreased following bevacizumab injection without ONC, remained at baseline after ONC, and increased slightly after ONC+bevacizumab. Histologically, there was a 38% RGC loss 21 days after ONC alone, which dropped to 14% with bevacizumab treatment; it was close to 15% with bevacizumab alone. Mean (SEM) microvascular perfusion in the optic nerve 4 days after ONC was significantly higher in the bevacizumab-treated (85% ± 10%) than the vehicle-treated (33% ± 13%) animals.
  
  
  CONCLUSIONS
  Bevacizumab treatment following ONC induction exerts a protective effect, manifested by reduced optic nerve head edema. The underlying mechanism probably involves a lesser interruption of axonal transport. Reduced expression of antioxidative and ischemic genes may contribute to RGC preservation.
authors.affiliation: Department of Ophthalmology, Kaplan Medical Center, Rehovot, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rappoport
authors.forename: Dana
authors.initials: D
authors.lastname: Morzaev
authors.forename: Shirel
authors.initials: S
authors.lastname: Weiss
authors.forename: Mark
authors.initials: M
authors.lastname: Vieyra
authors.forename: James D
authors.initials: JD
authors.lastname: Nicholson
authors.forename: Hana
authors.initials: H
authors.lastname: Leiba
authors.forename: Nitza
authors.initials: N
authors.lastname: Goldenberg-Cohen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068258:Bevacizumab; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009898:Optic Disk / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020221:Optic Nerve Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: bevacizumab; mouse model; neuroprotection; optic nerve crush