Effect Of Intravitreal Injection Of Bevacizumab On Optic Nerve Head Leakage And Retinal Ganglion Cell Survival In A Mouse Model Of Optic Nerve Crush

PURPOSE. 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 vertical bar 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.