Abstract
Purpose :
Celastrol,has been reported to anticancer, antiangiogenesis, and anti-invasive effect. However, it is still unclear whether Celastrol can alleviate neovascularization. Here, we investigated the potential effect of Celastrol on the hypoxia-induced retinal neovascularization and possible mechanisms.
Methods :
The C57BL/6J mice with oxygen-induced retinopathy were injected intravitreally with Celastrol (PBS, 1uM, 5uM per eye). Real-time PCR and western were used to determine the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA). In vitro, human umbilical vein endothelial cells(HUVECs) were used to study the proliferation, apoptosis, migration, tubular formation without (-) (control)or with (+) Celastrol (0.1%DMSO, 0.01uM, 0.1uM, 0.25uM) and/or VEGF(10ng/ml). Real-time PCR and western were used to determine the expression of HIF-1α and VEGFA.
Results :
Celastrol decreased the mRNA and protein expression of VEGFA and HIF-1α significantly (p<0.05) in mice compared with the control eyes. In a vitro system, the addition of Celastrol to the cell cultures attenuated the proliferation, scratch-wound healing and tube formation of vascular endothelial cells induced by VEGF(10ng/ml) significantly. Meanwhile, Celastrol decreased the protein expression of VEGFA and HIF-1α via inhibition of the AKT signaling pathway under hypoxia condition.
Conclusions :
Celastrol ameliorates retinal neovascularization through inhibition of the HIF-1α/VEGF signaling pathway. Our finding suggest that Celastrol is an antiangiogenic agent in pathophysiological settings and may be developed as a potential drug for the prevention and treatment of diabetic retinopathy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.