Activation of the innate immune system plays a major role in retinal degenerative diseases including age related macular degeneration (AMD). In this study, we investigated whether reactive microglia trigger and sustain NLRP3 inflammasome activation in human retinal pigment epithelium (ARPE-19) cells. Specifically, we analyzed the potential of cell culture supernatants from lipopolysaccharide (LPS)-stimulated human microglia in combination with the lysosomal destabilization agent Leu-Leu-O-Me (LLOMe) to activate the inflammasome in ARPE-19 cells. We found disorganization of ARPE-19 cytoskeletal structure after incubation with conditioned media of LPS-stimulated microglia and LLOMe and accumulation of lipid deposits in these cells using Nile Red staining. LC3-II, the active form of the'autophagy marker microtubule-associated protein 1 light chain 3 beta (LOB), was also elevated in ARPE-19 cells after inducing inflammasome activation. Finally, a significant increase of transcripts for IL -6, IL -8, IL -1 beta, GM-CSF and CCL-2 was detected in ARPE-19 stimulated with both microglia-conditioned medium and LLOMe. Our findings highlight a potential role of microglia in RPE inflammasome activation. (C ) 2017 Elsevier Inc. All rights reserved.