July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Salinomycin Inhibits TGFβ-induced RPE cell migration and contraction, key events in the pathogenesis of proliferative vitreoretinopathy
Author Affiliations & Notes
  • Jacob Proaño
    Flaum Eye Institute, University of Rochester Medical Center, New York, United States
    Lake Erie College of Osteopathic Medine, Erie, Pennsylvania, United States
  • Alison Heffer
    Flaum Eye Institute, University of Rochester Medical Center, New York, United States
  • Collynn Woeller
    Flaum Eye Institute, University of Rochester Medical Center, New York, United States
  • Steven E Feldon
    Flaum Eye Institute, University of Rochester Medical Center, New York, United States
  • Richard P Phipps
    Flaum Eye Institute, University of Rochester Medical Center, New York, United States
  • Ajay E. Kuriyan
    Flaum Eye Institute, University of Rochester Medical Center, New York, United States
  • Footnotes
    Commercial Relationships   Jacob Proaño, None; Alison Heffer, None; Collynn Woeller, None; Steven Feldon, None; Richard Phipps, None; Ajay Kuriyan, None
  • Footnotes
    Support  Research to Prevent Blindness (Flaum Eye Institute) and NIH P30EY001319-35
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5808. doi:
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      Jacob Proaño, Alison Heffer, Collynn Woeller, Steven E Feldon, Richard P Phipps, Ajay E. Kuriyan; Salinomycin Inhibits TGFβ-induced RPE cell migration and contraction, key events in the pathogenesis of proliferative vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5808.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Proliferative vitreoretinopathy (PVR) is a fibrotic process that is the most common cause of recurrent retinal detachment and associated with poor visual outcomes. Key pathologic processes in PVR development include retinal pigment epithelial (RPE) cell migration into the vitreous and along the retinal surface, and their subsequent contraction after undergoing epithelial-mesenchymal transition (EMT). Pharmacologic agents that inhibit RPE cell migration and contraction are potential treatments for PVR. We tested the ability of the polyether ionophore salinomycin to inhibit TGFβ-induced RPE cell migration and contraction.

Methods : We used both ARPE-19 and primary human RPE for all experiments. RPE cells were treated with 10 ng/ml TGFβ to induce migration and contraction, with or without 100-500nM salinomycin co-treatment for 72 hours. RPE cell migration was measured using a scratch assay. Collagen contraction assays were used to measure contraction of RPE cells embedded in a collagen matrix.

Results : We found that salinomycin inhibits TGFβ-induced ARPE-19 cell migration and contraction in vitro. The scratch assay demonstrated that TGFβ induced 100% wound closure in ARPE-19 cells after 72 hours. There was an inhibition of wound closure by 5% with 100nM salinomycin (p=0.01), 44% with 250nM salinomycin (p<0.0000), and 53% with 500 nM salinomycin (p<0.0000). TGFβ (10ng/ml) stimulation of ARPE-19 cells in a collagen matrix resulted in ~60% contraction of the collagen gel area after 72 hours, compared to 50% contraction with 100nM salinomycin (p=0.002), 36% contraction with 250nM salinomycin (p=0.02), and 28% contraction with 500 nM salinomycin (p=0.003). Primary human RPE cells showed a similar dose-dependent inhibition of TGFβ-induced RPE cell migration and contraction.

Conclusions : Salinomycin inhibits two major pathogenic processes in PVR: RPE cell migration and contraction. Further in vitro and in vivo studies are needed to evaluate SNC as a potential treatment for PVR.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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