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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
| Content Provider | Semantic Scholar |
|---|---|
| Author | Xue, Dong-Dong Lu, Bing-Zheng Li, Yuan Xin Sheng, Longxiang Zhou, Yuwei Zhang, Jing-Xia Lin, Gan-Jian Lin, Suizhen Yan, Guang-Mei Chen, Yupin |
| Copyright Year | 2019 |
| 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.3390/molecules24020252 |
| PubMed reference number | 30641903 |
| Journal | Medline |
| Volume Number | 24 |
| Alternate Webpage(s) | https://res.mdpi.com/molecules/molecules-24-00252/article_deploy/molecules-24-00252.pdf?attachment=1&filename= |
| Alternate Webpage(s) | https://doi.org/10.3390/molecules24020252 |
| Journal | Molecules |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
