Anti-inflammatory potential of simvastatin and amfenac in ARPE-19 cells; insights in preventing re-detachment and proliferative vitreoretinopathy after rhegmatogenous retinal detachment surgery

Niina Harju, Maria Hytti, Onni Kolari, Hilkka Nisula, Sirpa Loukovaara, Anu Kauppinen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Purpose: Rhegmatogenous retinal detachment is a severe vision-threatening complication that can result into proliferative vitreoretinopathy (PVR) and re-detachment of the retina if recovery from surgery fails. Inflammation and changes in retinal pigment epithelial (RPE) cells are important contributors to the disease. Here, we studied the effects of simvastatin and amfenac on ARPE-19 cells under inflammatory conditions. Methods: ARPE-19 cells were pre-treated with simvastatin and/or amfenac for 24 h after which interleukin (IL)-1α or IL-1β was added for another 24 h. After treatments, lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) processing, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity, prostaglandin E2 (PGE2) level, and extracellular levels of IL-6, IL-8, monocytic chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor, as well as the production of reactive oxygen species (ROS) were determined. Results: Pre-treatment of human ARPE-19 cells with simvastatin reduced the production of IL-6, IL-8, and MCP-1 cytokines, PGE2 levels, as well as NF-κB activity upon inflammation, whereas amfenac reduced IL-8 and MCP-1 release but increased ROS production. Together, simvastatin and amfenac reduced the release of IL-6, IL-8, and MCP-1 cytokines as well as NF-κB activity but increased the VEGF release upon inflammation in ARPE-19 cells. Conclusion: Our present study supports the anti-inflammatory capacity of simvastatin as pre-treatment against inflammation in human RPE cells, and the addition of amfenac complements the effect. The early modulation of local conditions in the retina can prevent inflammation induced PVR formation and subsequent retinal re-detachment.

Original languageEnglish
Article number158
JournalInternational Ophthalmology
Volume44
Issue number1
Number of pages14
ISSN0165-5701
DOIs
Publication statusPublished - 2024
MoE publication typeA1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Fields of Science

  • Amfenac
  • Inflammation
  • Proliferative vitreoretinopathy
  • Rhegmatogenous retinal detachment
  • RPE cells
  • Simvastatin
  • 3125 Otorhinolaryngology, ophthalmology

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