Clearance of autophagy-associated dying retinal pigment epithelial cells – a possible source for inflammation in age-related macular degeneration

M. Szatmári-Tóth, E. Kristóf, Z. Veréb, S. Akhtar, A. Facskó, L. Fésüs, A. Kauppinen, K. Kaarniranta, G. Petrovski

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and nonprofessional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.

Original languageEnglish
Article numbere2367
JournalCell Death and Disease
Volume7
Issue number9
DOIs
Publication statusPublished - Jan 1 2016

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Clearance of autophagy-associated dying retinal pigment epithelial cells – a possible source for inflammation in age-related macular degeneration'. Together they form a unique fingerprint.

  • Cite this