Effect of anti-VEGF antibody on retinal ganglion cells in rats.
OBJECTIVE
Intravitreal injection of anti-vascular endothelial growth factor (VEGF) antibody (bevacizumab, Avastin) has become one of the chief choices for the treatment of macular oedema and neovascular age-related macular degeneration. However, the effect of blocking the VEGF function has not been thoroughly explored in vivo. A previous study has reported that intravitreal injection of bevacizumab had no retinal toxicity on rats; however, bevacizumab is human-specific and does not react with rat VEGF. In this study, the authors examined the effect of anti-rat VEGF antibody and bevacizumab on rat retina 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 three days. The number of viable RGCs was counted. In vivo, after intravitreal injections of bevacizumab, anti-rat VEGF antibody, and control-IgG, viable RGCs were visualised by retrolabelling with Fluo-gold and enumerated to examine the toxicity.


RESULTS
In vivo, the mean (standard deviation) number of viable RGCs in the VEGF-treated group (0.99 (0.29) vs control), the bevacizumab-treated group (1.0 (0.23) vs control), the anti-rat VEGF antibody-treated group (0.98 (0.18) vs control) and the control IgG-treated group (0.98 (0.19) vs control) was not statistically different from that of the control group after 3 days. In vitro, the mean (SD) number of viable RGCs in the bevacizumab-treated group (2613 (230)/mm(2)), the anti-rat VEGF antibody-treated group (2600 (140)/mm(2)) and the control IgG-treated group (2656 (150)/mm(2)) was not statistically different from that of the control group (2656 (150)/mm(2)) after 7 days. There were no apparent histological abnormalities.


CONCLUSIONS
This study suggests that bevacizumab and anti-rat VEGF antibody have no short-term, direct retinal toxicity using the rat model. Intravitreal injection of bevacizumab shows no short-term, direct toxicity on RGCs.
Iriyama
Aya
A
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo 113-8655, Japan. akagi-tky@umin.ac.jp
Chen
Yi-Ning
YN
Tamaki
Yasuhiro
Y
Yanagi
Yasuo
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D007267:Injections; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab