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Xiaoling Liang, Boyu Yang, Yue Xu, Yaguang Hu, Xi Lu, Zhengjie Xu; Magnolol reduces retinal neovascularization in the OIR model and protects HUVECs under hypoxia via HIF-1a/VEGF pathway. Invest. Ophthalmol. Vis. Sci. 2017;58(8):200.
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To investigate whether Magnolol may reduce retinal neovascularization (RNV) in an oxygen-induced retinopathy (OIR) model and protect human umbilical vein endothelial cells (HUVECs) under hypoxia.
The neonatal C57BL/6J mice were exposed to 75% O2 from postnatal day (P) 7 to P12 and subsequently returned to room air. Mice were injected with 25mg/kg Magnolol intraperitoneally once a day from P12 to P17, then retinas were harvested and flat-mounted at P17 to assess the retinal vessels. To further explore the protective effect of Magnolol (20μM) on the HUVECs in vitro, cobalt chloride (CoCl2), a hypoxia-mimicking agent, was used to induce the hypoxia model. HUVECs were incubated with VEGF and CoCl2 in the presence or absence of Magnolol to perform the capillary-like tube formation assay. HUVECs migration was evaluated with wound healing assay. To clarify the molecular mechanisms of Magnolol, we observed the level of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF), which were assessed with immunofluorescence staining, RT-PCR and western blotting.
Magnolol significantly inhibited angiogenesis in vivo and in vitro evidenced by the reduction of RNV in OIR model and by the attenuation of hypoxia and VEGF-induced capillary tube-like structure formation of HUVECs, respectively. In addition, Magnolol inhibited hypoxia-induced HUVECs migration. In hypoxia, the expression of HIF-1α and VEGF in HUVECs were increased significantly. However, decreased levels of HIF-1α and VEGF were detected under hypoxia after Magnolol treatment.
These findings indicated that the anti-angiogenic activity of Magnolol is mediated by suppressing HIF-1a/VEGF-dependent pathways, and suggested that Magnolol might have potential for the treatment of pathological retinal angiogenesis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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