Fenofibric acid prevents retinal pigment epithelium disruption induced by interleukin-1β by suppressing AMP-activated protein kinase (AMPK) activation

M. Villarroel, M. Garcia-Ramírez, L. Corraliza, C. Hernández, R. Simó

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36 Citations (Scopus)

Abstract

Aims/hypothesis: The mechanisms involved in the beneficial effects of fenofibrate on the development and progression of diabetic macular oedema (DMO) remain to be elucidated. To shed light on this issue we have explored the effect of fenofibric acid on the barrier function of human retinal pigment epithelium (RPE) cells. Methods: ARPE-19 cells (a human RPE line) were cultured for 18 days under standard conditions and under conditions leading to the disruption of the monolayer (D-glucose, 25 mmol/l, with IL-1β, 10 ng/ml, added at days 16 and 17). Fenofibric acid, 25 μmol/l and 100 μmol/l, was added on the last 3 days of the experiment (one application/day). RPE cell permeability was evaluated by measuring apicalbasolateral movements of FITC-dextran (40 kDa). The production of tight junction proteins and AMP-activated protein kinase (AMPK) phosphorylation was assessed by western blot. Immunohistochemical studies of tight junction proteins and small interfering RNA transfection to AMPK were also performed in ARPE-19 monolayers. Results: Treatment of ARPE-19 cells with fenofibric acid significantly reduced the increment of permeability and the breakdown of the ARPE-19 cell monolayer induced by Dglucose, 25 mmol/l, and IL-1β, 10 ng/ml, in a dose-dependent manner. This effect was unrelated to changes in the content of tight junction proteins. Fenofibric acid prevented the activation of AMPK induced by IL-1β and the hyperpermeability induced by IL-1β was blocked by silencing AMPK. Conclusions/interpretation: Disruption of RPE induced by IL-1β is prevented by fenofibric acid through its ability to suppress AMPK activation. This mechanism could be involved in the beneficial effects of fenofibrate on DMO development. © Springer-Verlag 2011.
Original languageEnglish
Pages (from-to)1543-1553
JournalDiabetologia
Volume54
Issue number6
DOIs
Publication statusPublished - 1 Jun 2011

Keywords

  • AMPK
  • Blood-retinal barrier
  • Diabetic macular oedema
  • Diabetic retinopathy
  • Fenofibric acid
  • Il-1β
  • Permeability
  • Retinal pigment epithelium

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