Antiangiogenesis Effect of Albendazole on the Cornea

Abstract

Purpose: To investigate the anti-(lymph)angiogenic and anti-inflammatory effects of albendazole and to study whether these effects are additive with bevacizumab therapy in a murine corneal suture model. Methods: Corneal neovascularization (NV) and lymphangiogenesis (LY) were compared in a corneal suture model after administration of a subconjunctival injection of albendazole, bevacizumab, dexamethasone, or phosphate-buffered saline (PBS). Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction (RT-PCR) was performed to quantify the expression of inflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin-6), vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, and VEGFR-3. To evaluate the additive effect of albendazole, corneal NV and LY were also analyzed in a combined group of albendazole and bevacizumab therapy and the additive effect was compared with that in the group of double dose of bevacizumab. Results: The albendazole group showed less NV and less LY compared with the PBS control group (P < 0.01). When albendazole was combined with bevacizumab therapy, a significant decrease in NV and LY was seen compared with bevacizumab treatment alone, and with albendazole alone (all P values <0.05). The combination group showed better antilymphangiogenesis effect than the group of double dose bevacizumab. The albendazole-treated group showed reduced expression of VEGF-A, VEGF-C, TNF-alpha, and VEGFR-2 compared with corneas from the PBS group (P value <0.05 in all respective comparisons). Conclusion: Albendazole significantly decreased NV and LY in the cornea. This beneficial effect is additively enhanced when combined with bevacizumab treatment.

Keywords: albendazole; bevacizumab; lymphangiogenesis; neovascularization.