cGAS drives noncanonical-inflammasome activation in age-related macular degeneration

Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J Fowler, Elmira Baghdasaryan, Kenneth M Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R Hinton, Norbert Leitinger, John C Cambier, Joseph D Buxbaum, M Cristina Kenney, S Michal Jazwinski, Hiroshi Nagai, Isao Hara, A Phillip West, Katherine A Fitzgerald, SriniVas R Sadda, Bradley D Gelfand, Jayakrishna Ambati

Index: 10.1038/nm.4450

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Abstract

cGAS drives noncanonical-inflammasome activation in age-related macular degeneration cGAS drives noncanonical-inflammasome activation in age-related macular degeneration, Published online: 27 November 2017; doi:10.1038/nm.4450Degeneration of the retinal pigment epithelium is a hallmark of geographic atrophy, a type of age-related macular degeneration. Kerur et al. show that this degeneration results from a multistep pathway in which mitochondrial dysfunction in RPE cells, triggered by accumulation of Alu RNA, leads to activation of the noncanonical inflammasome via a cGAS–STING–IRF3 signaling axis.