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Molecules. 2019 Jan 11;24(2). pii: E252. doi: 10.3390/molecules24020252.

A Novel Synthetic Steroid of 2β,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia.

Author information

1
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Elinor_Sun@outlook.com.
2
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. xuedd@mail2.sysu.edu.cn.
3
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. lubzh3@mail2.sysu.edu.cn.
4
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. zmd2012spring@126.com.
5
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. shenglx@mail2.sysu.edu.cn.
6
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. zhuzhucute@163.com.
7
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. zhouyw7@mail2.sysu.edu.cn.
8
School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, China. zhjingx@mail.sysu.edu.cn.
9
Guangzhou Cellprotek Pharmaceutical Co. Ltd., G Building F/4, 3 Lanyue Road, Science City, Guangzhou 510663, China. linganjian@cellprotek.com.
10
Guangzhou Cellprotek Pharmaceutical Co. Ltd., G Building F/4, 3 Lanyue Road, Science City, Guangzhou 510663, China. linsuizhen@cellprotek.com.
11
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. ygm@mail.sysu.edu.cn.
12
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. chenyp39@mail.sysu.edu.cn.
13
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. yinwei@mail.sysu.edu.cn.

Abstract

Neuroinflammation has been well recognized as a key pathological event in acute glaucoma. The medical therapy of acute glaucoma mainly focuses on lowering intraocular pressure (IOP), while there are still scarce anti-inflammatory agents in the clinical treatment of acute glaucoma. Here we reported that β,3α,5α-trihydroxy-androst-6-one (sterone), a novel synthetic polyhydric steroid, blocked neuroinflammation mediated by microglia/macrophages and alleviated the loss of retinal ganglion cells (RGCs) caused by acute intraocular hypertension (AIH). The results showed that sterone significantly inhibited the morphological changes, the up-regulation of inflammatory biomarker ionized calcium-binding adapter molecule 1 (Iba-1), and the mRNA increase of proinflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in BV2 microglia and RAW264.7 macrophages. Moreover, immunofluorescence and western blotting analysis revealed that sterone markedly abrogated the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) p65 subunit. Furthermore, sterone significantly suppressed the inflammatory microglial activation and RGCs' reduction caused by retinal ischemia/reperfusion (I/R) injury in a rat AIH model. These results suggest sterone may be a potential candidate in the treatment of acute glaucoma caused by microglial activation-mediated neuroinflammatory injury.

KEYWORDS:

2β,3α,5α-trihydroxy-androst-6-one; acute glaucoma; ischemia/reperfusion injury; lipopolysaccharide; microglial activation; nuclear factor-κ B

PMID:
30641903
PMCID:
PMC6358879
DOI:
10.3390/molecules24020252
[Indexed for MEDLINE]
Free PMC Article

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