Article Text

other Versions

PDF
Retinal pigment epithelial cells display specific transcriptional responses upon TNF-α stimulation
  1. Nicoline M Korthagen1,
  2. Kiki van Bilsen2,
  3. Sigrid M A Swagemakers3,
  4. Jeroen van de Peppel2,
  5. Jeroen Bastiaans1,
  6. Peter J van der Spek3,
  7. P Martin van Hagen1,2,
  8. Willem A Dik1
  1. 1Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
  2. 2Department of Internal Medicine, Section Clinical Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
  3. 3Department of Bioinformatics, Erasmus MC, University Medical Center Rotterdam, The Netherlands
  1. Correspondence to Dr Willem A Dik, Department of Immunology, Laboratory Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands; w.dik{at}erasmusmc.nl

Abstract

Background/aims Tumour necrosis factor-α (TNF-α) is a key mediator of ocular inflammation and its interaction with the retinal pigment epithelium (RPE) may be a driving force in vitreoretinal disorders such as age-related macular degeneration, proliferative vitreoretinopathy (PVR) and diabetic retinopathy. Under inflammatory conditions, the ability of RPE cells to maintain the blood–retinal barrier and immune privilege may be lost and proliferation of RPE cells is facilitated. To gain insight into the effects of TNF-α on RPE cells, a gene expression study was performed.

Methods ARPE-19 and HT-29 cells were stimulated with 50 ng/mL TNF-α for 6 h. Gene expression patterns were compared between stimulated and control cells using whole genome gene expression arrays. Data were analysed using Partek and OmniViz and validated using quantitative RT-PCR. Functional annotation analysis was performed using Ingenuity and DAVID.

Results A total of 97 genes were uniquely modulated by TNF-α in ARPE-19 cells compared with HT-29 cells (86 upregulated and 11 downregulated). Most commonly affected biological processes were apoptosis, cell motility and cell signalling. The highest upregulated gene was EFNA1. Among the downregulated genes were transcription factors implicated in ocular development (SIX3, PAX6) and modulation of p53-mediated apoptosis (CITED2).

Conclusions This study provides insight into the unique responses of RPE cells to TNF-α stimulation and suggests a role for genes involved in apoptosis and retinal epithelial development. These findings contribute to our understanding of the behaviour of RPE cells under inflammatory conditions and the crucial role of RPE cells in vitreoretinal diseases.

  • Retina
  • Genetics
  • Inflammation

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • At a glance
    Keith Barton James Chodosh Jost Jonas