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Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration
- Source :
- Cell Death & Disease
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Cell
Gene Expression
Retinal Pigment Epithelium
Triamcinolone
Culture Media, Serum-Free
chemistry.chemical_compound
Macular Degeneration
0302 clinical medicine
Genes, Reporter
Elméleti orvostudományok
education.field_of_study
Chloroquine
Orvostudományok
Cell biology
medicine.anatomical_structure
Original Article
medicine.symptom
Microtubule-Associated Proteins
Programmed cell death
Immunology
Population
Green Fluorescent Proteins
Primary Cell Culture
Inflammation
Biology
Models, Biological
Cell Line
03 medical and health sciences
Cellular and Molecular Neuroscience
Phagocytosis
medicine
Autophagy
Humans
education
Retina
Interleukin-6
Adenine
Macrophages
Interleukin-8
Retinal
Cell Biology
Hydrogen Peroxide
eye diseases
Coculture Techniques
Oxidative Stress
030104 developmental biology
chemistry
Cell culture
030221 ophthalmology & optometry
sense organs
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....0b3d5437734ef0cb0e9a8906ad9058c5