Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration.
Citation:
Wooff Y, Fernando N, Wong JHC, Dietrich C, Aggio-Bruce R, Chu-Tan JA, Robertson AAB, Doyle SL, Man SM, Natoli R., Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration., Scientific reports, 10, 1, 2020, 2263Download Item:
Abstract:
Activation of the inflammasome is involved in the progression of retinal degenerative diseases, in particular, in the pathogenesis of Age-Related Macular Degeneration (AMD), with NLRP3 activation the focus of many investigations. In this study, we used genetic and pharmacological approaches to explore the role of the inflammasome in a mouse model of retinal degeneration. We identify that Casp1/11−/− mice have better-preserved retinal function, reduced inflammation and increased photoreceptor survivability. While Nlrp3−/− mice display some level of preservation of retinal function compared to controls, pharmacological inhibition of NLRP3 did not protect against photoreceptor cell death. Further, Aim2−/−, Nlrc4−/−, Asc−/−, and Casp11−/− mice show no substantial retinal protection. We propose that CASP-1-associated photoreceptor cell death occurs largely independently of NLRP3 and other established inflammasome sensor proteins, or that inhibition of a single sensor is not sufficient to repress the inflammatory cascade. Therapeutic targeting of CASP-1 may offer a more promising avenue to delay the progression of retinal degenerations.
Author's Homepage:
http://people.tcd.ie/doyles8Description:
PUBLISHED
Author: Doyle, Sarah
Type of material:
Journal ArticleCollections
Series/Report no:
Scientific reports;10;
1;
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Full text availableDOI:
http://dx.doi.org/10.1038/s41598-020-58849-zISSN:
2045-2322Metadata
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