Abstract
Purpose::
Intravitreal injection of anti-vascular endothelial growth factor (VEGF) antibody (bevacizumab and ranibizmab) has become one of the chief choices for the treatment of macular edema and neovascular age-related macular degeneration. However, the effect of blocking the VEGF function has not been thoroughly explored in vivo. Previous study reported that intravitreal injection of bevacizumab had no retinal toxicity on rat; however, bevacizumab is human-specific and does not react with rat VEGF. In this study, we examined the effect of anti-rat VEGF antibody and bevacizumab on rat retina both in vivo and in vitro, especially focusing on retinal ganglion cells (RGCs).
Methods::
In vitro, rat RGCs were purified by a two-step immunopanning procedure, and incubated in the presence of VEGF, bevacizumab, anti-rat VEGF antibody, and control-IgG for 3 days. The number of viable RGCs was counted. In vivo, after intravitreal injection of bevacizumab, anti-rat VEGF antibody, and control-IgG, viable RGCs was visualized by retrolabeling with Fluo-gold and enumerated to examine the toxicity.
Results::
In vivo, the number of viable RGCs in the VEGF-treated group (0.99 +/- 0.29 vs control), bevacizumab-treated group (1.0 +/- 0.23 vs control), anti-rat VEGF antibody-treated group (0.98 +/- 0.18 vs control) and control IgG-treated group (0.98 +/- 0.19 vs control) were not statically different from that of control group. In vitro, the numbers of viable RGCs in the bevacizumab-treated group (2613 +/- 230/mm2), anti-rat VEGF antibody-treated group (2600 +/- 140/mm2) and control IgG-treated group (2656 +/- 150/mm2) were not statically different from that of control group (2650 +/- 150/mm2). There were no apparent histological abnormalities.
Conclusions::
This study suggests that bevacizumab and anti-rat VEGF antibody have no retinal toxicity using rat model.
Keywords: age-related macular degeneration • drug toxicity/drug effects • retina