Triptolide attenuates laser-induced choroidal neovascularization via M2 macrophage in a mouse model.

Purpose: To investigate whether triptolide has inhibitory effects on the development of choroidal neovascularization (CNV), together with its underlying anti-angiogenic mechanisms.
Methods: CNV was induced in C57BL/6 J mice using laser photocoagulation. Triptolide at concentrations of 0.035 and 0.07 mg/kg body weight (BW) or the same volume of phosphate-buffered saline (PBS) was intraperitoneally injected into mice 2 days before laser photocoagulation, which was continued daily till the end of the experiment. CNV areas were measured on day 7. The numbers of M1, M2, and F4/80 ⁺ macrophages were detected on day 1, 3, and 7 in each group. The levels of vascular endothelial growth factor (VEGF) and inflammatory molecules,including intercellular adhesion molecule (ICAM)-1,tumor necrosis factor (TNF)-α, and interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay. Cell proliferation, migration, and tube-formation assays were performed in vitro.
Results: Triptolide at doses of 0.035 mg/kg BW (66,562 ± 39,253 μm ² , n = 5, P＜0.05) and 0.07 mg/kg BW (37,271 ± 25,182 μm ² , n = 5, P＜0.001) significantly reduced CNV areas by 54.9 and 74.8 %, respectively, compared with PBS control (147,699 ± 112,900 μm ² , n = 5) in a dose-dependent manner. Protein levels of VEGF, ICAM-1, TNF-α, and IL-6 in the RPE-choroid-sclera complex were significantly downregulated by triptolide treatment on day 3, which was in accordance with the reduced number of infiltrated F4/80 ⁺ macrophages and the reduced ratio of M2/F4/80 ⁺ macrophages. However, no toxic effects of triptolide on the retina or other systemic organs were observed. In addition, triptolide treatment exerted inhibitory effects on cell proliferation, migration, and tube formation in vitro in a concentration-dependent manner.
Conclusions: Triptolide has therapeutic potential in CNV owing to its anti-angiogenic effect.
(Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)