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K. H. Park, C. Kim, J. H. Kim, Y. S. Yu, H. Chung; Neuronal Toxicity of Intravitreal Bevacizumab in the Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5581.
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The latest studies show that vascular endothelial growth factor (VEGF) has neurotrophic and neuroprotective as well as angiogenic properties. The aim of this study is to investigate the neuronal toxicity of intravitreal bevacizumab in the retina in vivo and in vitro.
Human retinoblastoma cell (SNUOT-Rb1) viability test was performed using MTT assays after exposure for 24 hours to various concentrations of bevacizumab (0.125-2.5 mg/ml). Mouse retinal sections prepared at 1, 7, and 30 days after intravitreal injection of bevacizumab (Avastin, 25 mg/ml) into right eyes or normal saline (control) into left eyes were stained for histological analysis. Apoptotic cell death was determined using TUNEL assays. Retinal damage was assessed by immunolocalization studies using antibodies against neurofilament-light (NF-L).
The viabilities of SNUOT-Rb1 cells treated with bevacizumab at concentrations of up to 1.25 mg/ml were not significantly different from those of untreated control cells. However, at 2.5 mg/ml, viable cell numbers decreased significantly (P = 0.005). No evidence of histological toxicity was observed by light microscopy and no significant difference in apoptotic cell death and immunoreactivity with NF-L was observed between the bevacizumab-treated and control groups.
SNUOT-Rb1 cell viability assays and histological analysis, apoptotic cells assays and immunoreactivity with NF-L in the mouse retinal sections showed that intravitreal bevacizumab is safe and has no neuronal toxic effect. However, at higher doses (2.5 mg/ml) bevacizumab may be harmful to retinal neural cells, and thus, further studies are needed to clarify the side effects of intravitreal bevacizumab.
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