Abstract
Purpose :
Choroidal neovascularization (CNV) is the most important pathology leading to severe blindness in wet age-related macular degeneration (wAMD). At present, the main treatment for it is an intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. However, it can be a significant burden to the patient in terms of medical costs and invasiveness. Therefore, less burdensome treatment for wAMD is desired. Arctigenin is a natural lignan compound in Arctium lappa L and has many therapeutic effects including anti-inflammatory and vascular normalization. The aim of this study was to evaluate the effects of arctigenin on the CNV.
Methods :
We performed Cell Counting Kit-8 assay and Boyden chamber assay to investigate the effects of arctigenin on human retinal microvascular endothelial cells (HRMEC) proliferation and migration. The expression level of angiogenesis-related protein in HRMEC was assessed by western blotting. Additionally, we assessed the effect of arctigenin on mitochondrial respiratory change in HRMEC using a flux analyzer. In vivo study, we used the murine CNV model induced by laser photocoagulation in C57BL/6J mice. Arctigenin (100 mg/kg) was administrated orally once a day for 5 days before laser irradiation. To examine the effect of arctigenin on choroidal angiogenesis, the CNV area was quantified. We also evaluated macrophage accumulation around the CNV area by immunostaining of ionized calcium binding adaptor molecule 1 (Iba1).
Results :
Arctigenin (30 µM) suppressed cell proliferation and migration induced by VEGF in HRMEC. As the inhibitory mechanism of arctigenin, it was not to inhibit phosphorylation of VEGF receptor 2 but to inhibit phosphorylation of p38 in VEGF signaling. Arctigenin also inhibited basal respiration of mitochondria activated by VEGF. In vivo, oral administration of arctigenin (100 mg/kg) suppressed CNV formation and vascular leakage. In addition, orally administered arctigenin reduced macrophage accumulation around the CNV area.
Conclusions :
These findings suggest that the oral administration of arctigenin has beneficial effects on the CNV pathogenesis.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.