July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Triptolide inhibits experimental choroidal neovascularization in mice by modulating focal inflammatory microenvironment through macrophages
Author Affiliations & Notes
  • Kunbei Lai
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Yajun Gong
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Longhui Li
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Chuangxin Huang
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Fabao Xu
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Chenjin Jin
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Footnotes
    Commercial Relationships   Kunbei Lai, None; Yajun Gong, None; Longhui Li, None; Chuangxin Huang, None; Fabao Xu, None; Chenjin Jin, None
  • Footnotes
    Support  National Natural Science Foundation of China(81600741)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 362. doi:
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      Kunbei Lai, Yajun Gong, Longhui Li, Chuangxin Huang, Fabao Xu, Chenjin Jin; Triptolide inhibits experimental choroidal neovascularization in mice by modulating focal inflammatory microenvironment through macrophages. Invest. Ophthalmol. Vis. Sci. 2019;60(9):362.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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