Document Type
Article
Publication Date
12-21-2020
Abstract
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.
Recommended Citation
Heffer, Alison M.; Wang, Victor; Libby, Richard T.; Feldon, Steven E.; Woeller, Collynn F.; and Kuriyan, Ajay E., "Salinomycin inhibits proliferative vitreoretinopathy formation in a mouse model." (2020). Wills Eye Hospital Papers. Paper 134.
https://jdc.jefferson.edu/willsfp/134
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
33347461
Language
English
Comments
This is the final published article from the journal PLoS One, 2020 Dec 21;15(12):e0243626.
The article is also available on the journal's website: https://doi.org/10.1371/journal.pone.0243626
Copyright. The Authors.