July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Lipophilic simvastatin/atorvastatin prevent pro-inflammatory IL-6 and -8 cytokine response in RPE cells
Author Affiliations & Notes
  • Sirpa Loukovaara
    Ophthalmology, Helsinki University Central Hospital, Helsinki, Helsinki, Finland
  • Yashavanthi Mysore Mysore
    School of Pharmacy, School of Pharmacy, Faculty of Health Science, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio,, Kuopio, Kuopio, Finland
  • Anu Kauppinen
    School of Pharmacy, School of Pharmacy, Faculty of Health Science, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio,, Kuopio, Kuopio, Finland
  • Footnotes
    Commercial Relationships   Sirpa Loukovaara, None; Yashavanthi Mysore Mysore, None; Anu Kauppinen, None
  • Footnotes
    Support  Grant TYH2018127
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5723. doi:
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      Sirpa Loukovaara, Yashavanthi Mysore Mysore, Anu Kauppinen; Lipophilic simvastatin/atorvastatin prevent pro-inflammatory IL-6 and -8 cytokine response in RPE cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5723.

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

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Abstract

Purpose : Proliferative vitreoretinopathy is a complicated devastating intraocular pathology in which numerous proteins involved in cytoskeleton remodelling/cell metabolism/immune reactions play a role. In eyes with RRD, increased intravitreal proinflammatory, profibrotic, and proapoptotic protein expression levels may compromise post-surgical outcomes. Statins have recognized anti-inflammatory, anti-fibroproliferative, microvasculo-protective, and neuroprotective pleiotropic properties, rendering them as potential therapeutic adjuvants in controlling retinal wound-healing process/inflammation-related PVR formation in eyes after surgery for RRD (Kawahara et al. 2008). We studied the effect of lipophilic simvastatin/atorvastatin and hydrophilic rosuvastatin on pro-inflammatory interleukin (IL)-6 and -8 and monocyte activation MCP-1 levels in an experimental RPE culture model.

Methods : Human ARPE-19 cells. Viability was measured after 24 and 48 h statin exposure. Studied RPE cells were pre-treated either for 24h or 48h with statins and exposed thereafter to bacterial LPS for additional 24h. Levels of released IL-6, IL-8, and MCP-1 were determined from medium samples using the ELISA method.

Results : For lipophilic Simva and Atorva, 5 µM concentration was adequate to reduce the levels of IL-6, IL-8, or MCP-1 when ARPE-19 cells were pre-treated for 24h prior to the LPS-exposure. At 10 µM concentration, Atorva significantly reduced both IL-6 and IL-8 in 24h, whereas 48h pre-treatment was needed for significant reduction of IL-6 by Simva. Higher concentration (10 µM) Simva did not reduce IL-8 neither with 24h nor 48h treatment. Rosuvastatin (5 µM) significantly reduced the releases of IL-8 and MCP-1 when dissolved in water but not in DMSO. Simva at the concentration of 5-20 µM appeared to compromise the integrity of the cell membrane in 24h.

Conclusions : RPE cells play a central role in the development of various posterior segment eye disorders. Collectively, our results suggest that the secretion of IL-6, IL-8, and MCP-1 can be downregulated by lipophilic simvastatin/atorvastatin as well as hydrophilic rosuvastatin in RPE cells. Our experimental findings suggest that statin therapy could be used to decrease the risk of harmful PVR reaction in RRD as shown by previous clinical studies (Loukovaara et al. 2018). Further, pharmacological and in vitro-studies are needed to address open study questions.

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

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