July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Celastrol Inhibits pathological neovascularization in Oxygen-Induced Retinopathy Along with a Downregulation of HIF-1 and VEGFA Expression
Author Affiliations & Notes
  • Yaping Jiang
    Yangpu District Central Hospital, Shanghai, China
  • chuanxi Yang
    Jiangsu Province Hospital, Nanjing, China
  • Yihui Chen
    Yangpu District Central Hospital, Shanghai, China
  • Footnotes
    Commercial Relationships   Yaping Jiang, None; chuanxi Yang, None; Yihui Chen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5472. doi:
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      Yaping Jiang, chuanxi Yang, Yihui Chen; Celastrol Inhibits pathological neovascularization in Oxygen-Induced Retinopathy Along with a Downregulation of HIF-1 and VEGFA Expression. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5472.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

 

Celastrol affects endothelial cell function in vitro by wound-healing assay, tube formation and RTCA. **P<0.01(VEGF vs Ctrl), #P<0.05(VEGF vs VEGF+Celastrol 0.1μM), $P<0.05(VEGF vs VEGF+Celastrol 1μM),£P<0.05(VEGF vs VEGF+Celastrol 0.25 μM).

Celastrol affects endothelial cell function in vitro by wound-healing assay, tube formation and RTCA. **P<0.01(VEGF vs Ctrl), #P<0.05(VEGF vs VEGF+Celastrol 0.1μM), $P<0.05(VEGF vs VEGF+Celastrol 1μM),£P<0.05(VEGF vs VEGF+Celastrol 0.25 μM).

 

Figure2. Celastrol downregulates the protein and mRNA expression of HIF-1α and VEGFA in vivo and vitro.*Signicant difference compared with the hypoxia groups. #Signicant difference between the control groups.

Figure2. Celastrol downregulates the protein and mRNA expression of HIF-1α and VEGFA in vivo and vitro.*Signicant difference compared with the hypoxia groups. #Signicant difference between the control groups.

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