title: Absence of intravitreal bevacizumab-induced neuronal toxicity in the retina.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine & Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Cinoo
authors.initials: C
authors.lastname: Kim
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Park
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000367:Age Factors; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D007276:Injections, Intraventricular / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D012160:Retina / Q000166:cytology*; D012175:Retinoblastoma; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab