Inhibitory effect of intravitreal injection of bevacizumab on nerve growth factor

Abstract

Purpose: To investigate the inhibitory effect of intravitreal injection of bevacizumab on the expression of nerve growth factor (NGF) in rabbit retina.

Methods: The right eyes of 40 New Zealand white rabbits were injected with 1.25 mg (0.05 cc) bevacizumab three times monthly; as controls, the left eyes received sham injections. Apoptosis in retinal cells was evaluated by immunohistochemical staining for caspase-3, and by in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. NGF and vascular endothelial growth factor (VEGF) proteins in rabbit retinas were measured quantitatively (Enzyme linked immunosorbent assay (ELISA)) and qualitatively (immunohistochemical staining) 1 and 4 months after injection. NGF and VEGF messenger RNAs in rabbit retinas were evaluated by real-time polymerase chain reaction (RT-PCR).

Results: As shown by the TUNEL assay and caspase-3 immunostaining, the bevacizumab-injected group had significantly more apoptotic activity than did the control group. Levels of retinal NGF and VEGF proteins in the bevacizumab group were lower than those in the control group (p < 0.05). Immunohistochemical staining of NGF and VEGF was weaker in the bevacizumab group than in the control group. NGF and VEGF mRNA levels in the bevacizumab group were lower than those of the control group (p < 0.05).

Conclusions: Findings of the present study suggest that apoptosis in retinal cells after intravitreal bevacizumab injection is increased by down-regulated NGF, caused by VEGF inhibition in rabbits.