Abstract
Purpose :
Inflammation plays an important role in the development of choroidal neovascularization (CNV). Triptolide, an anti-inflammatory diterpenoid epoxide produced by Tripterygium wilfordii, is potentially antiangiogenic material for CNV. To investigate the effects of Triptolide on the development of CNV, together with its underlying anti-inflammatory mechanisms.
Methods :
Experimental CNV was induced by laser photocoagulation in C57BL/6J mice, followed by intraperitoneal injection of Triptolide at the doses of 0.035, 0.07 mg/kg BW or the same volume of vehicle daily. Seven days after treatment, mice were sacrificed and the sizes of CNV areas were measured using the choroidal flatmount technique. Numbers of infiltrated polarized macrophages, protein levels of VEGF, as well as inflammatory molecules including ICAM-1, TNF-α, and IL-6 in the RPE-choroid complex were detected 3 days and 7 days after laser photocoagulation. The role of Notch signaling pathway in macrophage polarization regulating by Triptolide was also investigated. Effects of Triptolide on endothelial cell migration and tube formation were also studied. Toxicity of Triptolide was evaluated in vivo and in vitro.
Results :
Areas of CNV were significantly suppressed by Triptolide treatment without toxicity compared with vehicle treatment in a dose-dependent manner: Triptolide treatment of 0.035 mg/kg BW (66562 ± 39253 μm2, p<0.01) and 0.07 mg/kg BW (37271 ± 25182 μm2, p<0.01) suppressed the development of CNV by 54.9% and 74.8% compared with the control group (147699 ± 112900 μm2), respectively. Triptolide treatment modulated macrophage polarization and downregulated protein expressions of VEGF, ICAM-1, TNF- α, and IL-6. Moreover, Triptolide upregulated downstream proteins of Notch signaling pathway including Hes-1, Hey-1. Triptolide also showed an inhibitive effect on cell proliferation and migration and capillary-like tube formation of endothelial cells.
Conclusions :
Anti-inflammatory treatment with triptolide might be a novel chemical therapy for CNV-related diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.