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Yi Liao, Yalin Wu; NLRP3 inflammasome activation by all-trans-retinaldehyde underlies the degeneration of retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1929.
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© ARVO (1962-2015); The Authors (2016-present)
Visual (retinoid) cycle anomaly induced aberrant buildup of all-trans-retinaldehyde (atRAL) is incriminated as the cause of retinal pigment epithelium (RPE) atrophy in Stargardt disease (STGD) and age-related macular degeneration (AMD). NLRP3 inflammasome activation is also considered to implicate with the etiology of AMD. Accordingly, we aimed to elucidate the relationship between atRAL and NLRP3 inflammasome activation in RPE cells.
Cellular toxicities were assayed by MTT or MTS assay. Protein levels of NLRP3, ASC, Caspase-1 p20, pro-IL-1β, and pro-IL-18 were measured by Western blotting. Secreted IL-1β and IL-18 in culture supernatant were analyzed by immunoblotting and multiplex assay and enzyme-linked immunosorbent assay (ELISA). Cellular uptake, subcellular localization, lysosomal alkalinization, and Caspase-1 activity were detected by fluorescence microscope. Ultrastructure of mitochondria, lysosomes and endoplasmic reticulum were examined by transmission electron microscope.
atRAL elevated the expression of NLRP3 inflammasome related genes as well as NLRP3 protein in primary porcine RPE cells and human RPE cell line ARPE-19. Moreover, after treating ARPE-19 cells with atRAL, apoptosis and pyroptosis were triggered, and reactive oxygen species (ROS) produced from mitochondria and cathepsins released from lysosomes transmitted the signals for NLRP3 inflammasome activation.
Our results demonstrate that atRAL that accumulates beyond a threshold promotes RPE degeneration via activating NLRP3 inflammasome.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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