Salinomycin inhibits proliferative vitreoretinopathy formation in a mouse model.
Salinomycin inhibits proliferative vitreoretinopathy formation in a mouse model.
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DOI：
10.1371/journal.pone.0243626
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Kuriyan AE
中科院分区：
文献类型：
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作者：
Heffer AM;Wang V;Libby RT;Feldon SE;Woeller CF;Kuriyan AE
Proliferative vitreoretinopathy (PVR) is a progressive disease that develops in a subset of patients who undergo surgery for retinal detachment repair, and results in significant vision loss. PVR is characterized by the migration of retinal pigment epithelial (RPE) cells into the vitreous cavity, where they undergo epithelial-to-mesenchymal transition and form contractile membranes within the vitreous and along the retina, resulting in recurrent retinal detachments. Currently, surgical intervention is the only treatment for PVR and there are no pharmacological agents that effectively inhibit or prevent PVR formation. Here, we show that a single intravitreal injection of the polyether ionophore salinomycin (SNC) effectively inhibits the formation of PVR in a mouse model with no evidence of retinal toxicity. After 4 weeks, fundus photography and optical coherence tomography (OCT) demonstrated development of mean PVR grade of 3.5 (SD: 1.3) in mouse eyes injected with RPE cells/DMSO (vehicle), compared to mean PVR grade of 1.6 (SD: 1.3) in eyes injected with RPE cells/SNC (p = 0.001). Additionally, immunohistochemistry analysis showed RPE cells/SNC treatment reduced both fibrotic (αSMA, FN1, Vim) and inflammatory (GFAP, CD3, CD20) markers compared to control RPE cells/DMSO treatment. Finally, qPCR analysis confirmed that Tgfβ, Tnfα, Mcp1 (inflammatory/cytokine markers), and Fn1, Col1a1 and Acta2 (fibrotic markers) were significantly attenuated in the RPE cells/SNC group compared to RPE/DMSO control. These results suggest that SNC is a potential pharmacologic agent for the prevention of PVR in humans and warrants further investigation.
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DOI：
10.2174/1871520615666150101130209
发表时间：
2015-01-01
影响因子：
2.8
作者：
Antoszczak, Michal;Huczynski, Adam
通讯作者：
Huczynski, Adam
影响因子：
2.1
作者：
BAUDOUIN, C;FREDJREYGROBELLET, D;GASTAUD, P
通讯作者：
GASTAUD, P
影响因子：
4.1
作者：
HISCOTT, PS;GRIERSON, I;MCLEOD, D
通讯作者：
MCLEOD, D
影响因子：
3.6
作者：
Hansen TC;Woeller CF;Lacy SH;Koltz PF;Langstein HN;Phipps RP
通讯作者：
Phipps RP
TGFβ 信号的背景
DOI：
10.1038/nrm3434
发表时间：
2012-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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