2017
DOI: 10.1016/j.yexcr.2017.08.012
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A novel RIPK1 inhibitor that prevents retinal degeneration in a rat glaucoma model

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Cited by 37 publications
(30 citation statements)
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“…In conclusion, we have demonstrated that RGC death signaling pathways are active in a regionspecific manner after blunt ocular injury, with necroptotic-dependent mechanisms likely driving a reduction in RGC numbers at the center of the impact site. The inhibition of necroptosis using pharmacological inhibitor, Nec-1s, preserved the number of RBPMS + and BRN3A + RGC compared to In line with our findings, RGC are also protected by the inhibition of necroptosis in other models of RGC death, including glaucoma [62] and retinal ischemia-reperfusion injury [63], and other models of neuronal disease and degeneration, including amyotrophic lateral sclerosis [64][65][66], Alzheimer's disease [26], Niemann-Pick disease [67], traumatic brain injury [28] and spinal cord injury [27]. The abundance of studies across multiple disease indicates the importance of necroptotic signaling in driving neuronal cell death.…”
Section: Discussionsupporting
confidence: 89%
“…In conclusion, we have demonstrated that RGC death signaling pathways are active in a regionspecific manner after blunt ocular injury, with necroptotic-dependent mechanisms likely driving a reduction in RGC numbers at the center of the impact site. The inhibition of necroptosis using pharmacological inhibitor, Nec-1s, preserved the number of RBPMS + and BRN3A + RGC compared to In line with our findings, RGC are also protected by the inhibition of necroptosis in other models of RGC death, including glaucoma [62] and retinal ischemia-reperfusion injury [63], and other models of neuronal disease and degeneration, including amyotrophic lateral sclerosis [64][65][66], Alzheimer's disease [26], Niemann-Pick disease [67], traumatic brain injury [28] and spinal cord injury [27]. The abundance of studies across multiple disease indicates the importance of necroptotic signaling in driving neuronal cell death.…”
Section: Discussionsupporting
confidence: 89%
“…Increasing evidence has demonstrated the importance of necroptosis in retinal cell death (Cai et al, 2015;Do et al, 2017;Dvoriantchikova et al, 2014;Shosha et al, 2016); therefore, we examined the effect of Epac1 deletion on necroptosis. At the molecular level, necroptosis is reported to be regulated by receptor-interacting protein 3 (RIP3), whose activation is tightly regulated by phosphorylation.…”
Section: Resultsmentioning
confidence: 99%
“…Having explored the cellular consequences of intravitreal TNF-α injection, we next investigated activation of pro-degenerative molecular pathways. TNF-α can trigger apoptosis or necroptosis in different contexts, including in promoting RGC death in models of glaucoma (Fuchs and Steller, 2015;Weinlich et al, 2017;Do et al, 2017;Almasieh et al, 2012). Hence, we used immunoblotting to assess molecular markers of apoptosis and necroptosis in the optic nerve following intravitreal TNF-α injection.…”
Section: Tnf-α Induces Sarm1-dependent Axon Loss and Rgc Death In A Nmentioning
confidence: 99%