Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 12, Issue 11, Pages 1363-1371Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.16334
Keywords
Aloe-emodin; vascular endothelial growth factor; angiogenesis; hypoxia-inducible factor-1; oxygen-induced retinopathy
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Funding
- Technology Support Program of Science and Technology Department of Sichuan Province, China [2012SZ0038]
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Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory effect of AE on the hypoxia-induced retinal neovascularization and the possible mechanisms. Methods: We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 mu M CoCl2 to the ARPE-19 cells, then treated the cells with different concentrations of AE (0.2, 1.0 and 5.0 mu g/mL) or a special hypoxia-inducible factor 1 alpha (HIF-1 alpha) inhibitor [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, YC-1, 1.0 mu g/mL]. The cellular supernatants were collected 48 h later to measure the VEGFA concentrations by human VEGFA enzyme-linked immunosorbent assay (ELISA) kits, the mRNA expressions of VEGFA, HIF-1 alpha and prolyl hydroxylase-2 (PHD-2) by quantitative reverse transcription-PCR (qRT-PCR) and the protein expressions of HIF-1 alpha and PHD-2 by Western blots. For in vivo study, the rat pups with oxygen-induced retinopathy were treated with Conbercept ophthalmic injection (1.0 mg/kg) or AE (5.0 and 10.0 mg/kg) for five days, then the retinal avascular areas were assessed via visualization of the retinal vasculature with ADPase and hematoxylin & eosin (H&E) stains. Results: AE inhibits the VEGFA secretion of ARPE-19 cells under hypoxia condition, decreases the mRNA expressions of VEGFA and PHD-2 and the protein expressions of VEGFA, HIF-1 alpha and PHD-2 in vitro and prevents hypoxia-induced retinal neovascularization in vivo. Conclusions: AE ameliorates retinal neovascularization throuth inhibition of the HIF-1 alpha/VEGF signaling pathway. AE may be developed as a potential drug for the prevention and treatment of diabetic retinopathy.
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