Absence of intravitreal bevacizumab-induced neuronal toxicity in the retina

Bevacizumab is a complete humanized monoclonal antibody directed against all isoforms of vascular endothelial growth factor (VEGF). It was originally used as a first-line treatment for metastatic colorectal cancer. Recently, intravitreal bevacizumab has been effectively applied to vasoproliferative diseases, such as retinal and choroidal neovascularization. However, it is known that intravenous administration of bevacizumab in the treatment of cancer can lead to serious adverse events, such as congestive heart failure, thromboembolism, and neuropathy. In this study, we showed that very high concentrations of intravitreal bevacizumab, even up to 15 times the dose normally used in human clinical applications, (1microl, 25mg/ml), caused no definite histological abnormalities and no significant increase in apoptotic cell death in the mouse retina at 4 weeks after treatment. Moreover, intravitreal bevacizumab induced no neuronal toxicity in the retina. Even in high concentrations, bevacizumab caused no changes in the viability of retinal neurons or the expression of neurofilament, a marker of neuronal differentiation. Therefore, we believe that intravitreal bevacizumab has therapeutic potential for the treatment of retinal and choroidal neovascularization and has the added benefit of exhibiting no acute or chronic toxicity in retinal neurons.This study was supported by R01-2004-000-10212-0 from the Basic Research Program of the Korea Science & Engineering Foundation and by the Bio-signal Analysis Technology Innovation Program (M1064501001-06n4501-00110) of the Ministry of Science and Technology (MOST) and the Korea Science and Engineering Foundation (KOSEF)