Bevacizumab neutralizes the protective effect of vascular endothelial growth factor on retinal ganglion cells

PURPOSE: Vascular endothelial growth factor (VEGF) is well known for its role in pathologic neovascularization, including wet age-related macular degeneration. However, a growing body of evidence indicates that VEGF is also neuroprotective of non-vascular cells in various animal models through reduction of oxidative stress. In light of the widespread use of intraocular anti-VEGF therapies for age-related macular degeneration (AMD), we evaluated the impact of anti-VEGF agents on the neuroprotective effect of VEGF on retinal ganglion cells. METHODS: Staurosporine differentiated retinal ganglion cells were treated with increasing doses of VEGF in the presence of hydrogen peroxide. After optimization, an increasing concentration of bevacizumab was added to neutralize VEGF-mediated protection. The degree of oxidative damage was measured at various time points using buthionine sulfoxime (BSO), a glutathione reductase inhibitor. Cell viability was assessed using WST-1 and Crystal violet assays. RESULTS: VEGF (200 ng/ml) protected differentiated retinal ganglion cells (RGC)-5 against H(2)0(2)-mediated oxidative stress. This effect was eliminated by co-treatment with bevacizumab (2.0 mg/ml), which by itself was not cytotoxic. CONCLUSIONS: These results indicate an important role for VEGF in the maintenance of retinal ganglion cells.