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RESEARCH PRODUCT

Inflammatory cytokines decrease viability and alter ganglioside profile in retinal pigment epithelium cells

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Purpose Early stages of Age related Macular Degeneration (AMD) are characterized by dysfunction and degeneration of the retinal pigment epithelium (RPE) cells, which participate in the death of the overlying photoreceptors ultimately leading to loss of vision. Gangliosides (GG) make a wide and heterogeneous family of sialic-acid-containing glycosphingolipids, composed of a sugar chain branched on a ceramide. They are major components of cellular membranes, particularly abundant in the brain and nervous tissue, including retina. While their developmental and neuroprotective actions have been demonstrated, their precise role in retina’s function and its pathologies is still poorly understood. The present study aimed to investigate the role of GG in the response of RPE cells to inflammation, which is known as one of the pathophysiological features of AMD. Methods Cultured human RPE cells (ARPE19) were exposed to an inflammatory cytokine mixture (ICM): TNF-α, IL-1β and IFN-g for 72 hours. Cell viability was assessed and GG were analyzed by Liquid Chromatography coupled with tandem mass spectrometry. Results ICM had deleterious effects on ARPE19 viability: cell number decreased by half between control and treated conditions. GM3 appeared to be the main GG class present in ARPE19 cells. Interestingly, ICM exposure was associated with modifications in the GM3 profile: relative amounts d18:1/16:0 species increased whereas those of d18:1/24:1 species decreased. Conclusion Our observations suggest that GG might be implicated in ARPE19 cell response to inflammatory cytokines, although the precise biological role of the change in fatty acid profile of GM3 still needs to be clarified.