Effect of intravitreal injection of bevacizumab on optic nerve head leakage and retinal ganglion cell survival in a mouse model of optic nerve crush

• Published in: Investigative ophthalmology & visual science 2013-12, Vol.54 (13), p.8160-8171
• Main Authors: Rappoport, Daniel, Morzaev, Dana, Weiss, Shirel, Vieyra, Mark, Nicholson, James D, Leiba, Hana, Goldenberg-Cohen, Nitza
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacokinetics; Animals; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - pharmacokinetics; Bevacizumab; Cell Survival - drug effects; Disease Models, Animal; Fluorescein Angiography; Fundus Oculi; Immunohistochemistry; Intravitreal Injections; Male; Mice; Mice, Inbred C57BL; Optic Disk - drug effects; Optic Disk - metabolism; Optic Disk - pathology; Optic Nerve Injuries - complications; Optic Nerve Injuries - drug therapy; Optic Nerve Injuries - pathology; Retinal Degeneration - etiology; Retinal Degeneration - pathology; Retinal Degeneration - prevention & control; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Treatment Outcome; Vascular Endothelial Growth Factor A - antagonists & inhibitors
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.13-12771

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). 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. 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. 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.