Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration
Date
2020
Authors
Wooff, Yvette
Fernando, Nilisha
Wong, Josephine
Dietrich, Catherine
Aggio-Bruce, Riemke
Chu-Tan, Joshua
Robertson, Avril
Doyle, Sarah
Man, Si Ming
Natoli, Riccardo
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Volume Title
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Nature Publishing Group
Abstract
Activation of the infammasome 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 infammasome in a mouse model of retinal degeneration. We identify that Casp1/11−/−
mice have better-preserved retinal function, reduced infammation 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 infammasome sensor proteins, or that inhibition of a single sensor is not sufcient to
repress the infammatory cascade. Therapeutic targeting of CASP-1 may ofer a more promising avenue
to delay the progression of retinal degenerations.
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Scientific Reports
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Journal article
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Open Access
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Creative Commons Attribution 4.0 International License
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