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

21 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 non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.

Original languageEnglish
Pages (from-to)e2367
JournalCell death & disease
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 8 2016

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Retinal Pigments
Autophagy
Macular Degeneration
Epithelial Cells
Inflammation
Cell Death
Macrophages
Dendritic Cells
Triamcinolone
Chloroquine
Phagocytes
Interleukin-8
Hydrogen Peroxide
Glucocorticoids
Retina
Interleukin-6
Electron Microscopy
Oxidative Stress
Light
Serum

ASJC Scopus subject areas

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

Cite this

Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration. / Szatmári-Tóth, M.; Kristóf, E.; Veréb, Z.; Akhtar, S.; Facskó, A.; Fésüs, L.; Kauppinen, A.; Kaarniranta, K.; Petrovski, G.

In: Cell death & disease, Vol. 7, No. 9, 08.09.2016, p. e2367.

Research output: Contribution to journalArticle

Szatmári-Tóth, M. ; Kristóf, E. ; Veréb, Z. ; Akhtar, S. ; Facskó, A. ; Fésüs, L. ; Kauppinen, A. ; Kaarniranta, K. ; Petrovski, G. / Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration. In: Cell death & disease. 2016 ; Vol. 7, No. 9. pp. e2367.
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