Antimycin A-induced mitochondrial dysfunction regulates inflammasome signaling in human retinal pigment epithelial cells

Age-related macular degeneration (AMD) is a severe retinal eye disease where dysfunctional mitochondria and damaged mitochondrial DNA in pigment epithelium (RPE) have been demonstrated to underlie the pathogenesis of this devastating disease. In present study, we aimed examine whether induce inflammasome activation human RPE cells. Therefore, ARPE-19 cells were primed with IL-1α exposed electron transport chain complex III inhibitor, antimycin A. We found that A-induced dysfunction caused caspase-1-dependent subsequent production mature IL-1β IL-18 AIM2 NLRP3 appeared be responsible receptors upon damage. at verifying our findings using hESC-RPE but A was absorbed by melanin. results repeated on D407 cell cultures. Antimycin NADPH oxidase-dependent ROS occurred upstream activation, whereas K+ efflux not required for A-treated Collectively, data emphasize regulate assembly multiprotein complexes The study associates AMD.