2013
DOI: 10.1167/iovs.12-10655
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NLRP3 Inflammasome Activation in Retinal Pigment Epithelial Cells by Lysosomal Destabilization: Implications for Age-Related Macular Degeneration

Abstract: NLRP3 upregulation occurs in the RPE during the pathogenesis of advanced AMD, in both geographic atrophy and neovascular AMD. Destabilization of RPE lysosomes induces NLRP3 inflammasome activation, which may contribute to AMD pathology through the release of the proinflammatory cytokine IL-1β and through caspase-1-mediated cell death, known as "pyroptosis."

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Cited by 252 publications
(335 citation statements)
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“…Numerous studies have established a role for NLRP3 inflammasome in promoting inflammation and RPE damage in response to factors associated with macular degeneration such as lysosomal destabilization (Tseng et al, 2013), oxidative stress (Kauppinen et al, 2012), and Alu RNA (Tarallo et al, 2012). The present study highlights drusen component Aβ as an important stimulus for inflammasome activation in the RPE, in keeping with similar observation of Aβ's effect in microglia (Halle et al, 2008).…”
Section: Discussionsupporting
confidence: 88%
“…Numerous studies have established a role for NLRP3 inflammasome in promoting inflammation and RPE damage in response to factors associated with macular degeneration such as lysosomal destabilization (Tseng et al, 2013), oxidative stress (Kauppinen et al, 2012), and Alu RNA (Tarallo et al, 2012). The present study highlights drusen component Aβ as an important stimulus for inflammasome activation in the RPE, in keeping with similar observation of Aβ's effect in microglia (Halle et al, 2008).…”
Section: Discussionsupporting
confidence: 88%
“…Combined data from three experiments are shown as mean ± SEM. ** denotes P < 0.01 and *** P < 0.001, Mann-Whitney U-test retinal pigment epithelial (RPE) cells (Tseng et al 2013), and it seems to act similarly also in HUVECs.…”
Section: Discussionmentioning
confidence: 99%
“…The inflammasome is a multiprotein complex comprising a sensor protein, the adaptor protein ASC (apoptosisassociated speck-like domain containing caspase recruitment domain), and the inflammatory protease caspase-1. The eye has many inflammasome-forming sensors 49 including NLRP receptor molecules (nucleotidebinding domain and leucine-rich repeat containing pyrin domain family). Inflammasome-dependent biological effects may be mediated not only by IL-1b and IL-18, but also by the multifaceted activities of caspase-1.…”
Section: Understanding Uveitismentioning
confidence: 99%