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The Nrf2 inhibitor brusatol has a protective role in a rat model of oxygen-induced retinopathy of prematurity

Published online by Cambridge University Press:  17 March 2021

Xiuying Liang  and
Ruifen Wang
Xiuying Liang*
Affiliation:
Department of Neonatology, Cangzhou Central Hospital of Hebei Province, Cangzhou, Hebei, China
Ruifen Wang
Affiliation:
Department of Neonatology, Cangzhou Central Hospital of Hebei Province, Cangzhou, Hebei, China
*
*Address correspondence to: Xiuying Liang, E-mail: liangxiuying0608@sina.com
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Abstract

Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been testified to be involved in the development of retinopathy of prematurity (ROP), which can cause childhood visual impairment. Whether brusatol, an Nrf2 inhibitor, could be utilized to treat ROP was unknown. The oxygen-induced retinopathy rat model was established to mimic ROP, which was further intravitreal administrated with brusatol. Vessel morphology and microglial activation in the retina were assessed with histology analysis. The relative expression levels of angiogenesis and inflammation-related molecules were detected with Western blot and real-time polymerase chain reaction methods. Intravitreal brusatol administration could alleviate both angiogenesis and microgliosis induced by hyperoxia, along with down-regulation of vascular endothelial growth factor, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, cluster of differentiation molecule 11B, tumor necrosis factor alpha, inducible nitric oxide synthase, glial fibrillary acidic protein, and IBA-1 expression. It was further revealed that Nrf2 and heme oxygenease-1 were diminished by brusatol administration. The results demonstrate the potential of intravitreal brusatol deliver to treat ROP with down-regulation of angiogenesis and microgliosis.

Keywords

Nrf2brusatoloxygen-induced retinopathyretinopathy of prematurity
Type
Research Article
Information
Visual Neuroscience , Volume 38 , 2021 , E002
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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