Abstract | PURPOSE: METHODS: RESULTS:
Inflammasome activation in RPE cells was associated with caspase-1-dependent secretion of IL-1β, IL-6, IL-18, GM-CSF, and GRO (CXCL1/2/3), whereas constitutive secretion of VEGF was reduced. Secretion of IL-1β and IL-18 was highly polarized to the apical cell side. Incubation with conditioned media of inflammasome-activated RPE cells induced directed migration of microglia cells (11.0-fold increase) and diminished vascular endothelial cells proliferation (39.0% reduction) and migration (69.3% reduction) as compared with conditioned media of untreated control RPE cells. CONCLUSIONS: Lysosomal membrane permeabilization-induced activation of the NLRP3 inflammasome in RPE cells results in apical secretion of inflammatory cytokines with chemotactic effects on microglia cells and reduced constitutive secretion of VEGF. Via these mechanisms, lipofuscin phototoxicity may contribute to local immune processes in the outer retina as observed in AMD.
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Authors | Lena K M Mohr, Andrea V Hoffmann, Carolina Brandstetter, Frank G Holz, Tim U Krohne |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 56
Issue 11
Pg. 6404-13
(Oct 2015)
ISSN: 1552-5783 [Electronic] United States |
PMID | 26444721
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- Inflammasomes
- Vascular Endothelial Growth Factor A
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Topics |
- Animals
- Cells, Cultured
- Cytokines
(metabolism)
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Humans
- Immunity, Innate
- Inflammasomes
(physiology)
- Macular Degeneration
(immunology, metabolism, pathology)
- Mice
- Retinal Pigment Epithelium
(immunology, metabolism, pathology)
- Vascular Endothelial Growth Factor A
(metabolism)
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