Erythropoietin protects retinal pigment epithelial cells against the increase of permeability induced by diabetic conditions: Essential role of JAK2/ PI3K signaling

Marta Garcia-Ramírez, Cristina Hernández, Marisol Ruiz-Meana, Marta Villarroel, Lidia Corraliza, David García-Dorado, Rafael Simó

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27 Citations (Scopus)

Abstract

The outer blood-retinal barrier is formed by retinal pigment epithelial (RPE) cells and its disruption significantly contributes to the development of diabetic macular edema (DME). The aim of the study was to explore whether erythropoietin (Epo) has beneficial effects on the barrier function of human RPE cells and the main downstream pathways involved. ARPE-19 cells were cultured in standard conditions and under conditions leading to the disruption of the monolayer [25mmol/L d-glucose plus IL-1β (10ng/mL)]. Epo (200mU/mL/day) was added during the last 2days of the experiment. The experiments were repeated in the presence of an Epo neutralizing antibody and specific inhibitors of JAK2 and PI3K (AG490 and LY294002, respectively). Permeability was evaluated by fluorescein isothiocyanate dextran (70kDa) movements. Distribution of tight junction proteins was examined by immunofluorescence. Changes in cytosolic Ca 2+ induced by Epo were also measured. Epo treatment was able to prevent but not to restore the increase of permeability induced by high glucose plus IL-1β. The protective effect of Epo on RPE barrier function was completely blocked by AG490 and almost completely abolished by LY294002. In addition, Epo was able to increase cytosolic Ca 2+ with dependence on extracellular calcium influx and this effect was blocked by either JAK2 or PI3K inhibition. We conclude that RPE disruption induced by high glucose plus IL-1β is prevented by Epo through the downstream signaling of JAK2 and PI3K/AKT pathways. © 2011 Elsevier Inc.
Original languageEnglish
Pages (from-to)1596-1602
JournalCellular Signalling
Volume23
Issue number10
DOIs
Publication statusPublished - 1 Oct 2011

Keywords

  • Diabetic macular edema
  • Erythropoietin
  • JAK2
  • Permeability
  • PI3K/AKT
  • Retinal pigment epithelial cells

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