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Keiko Kataoka, Hidetaka Matsumoto, Kimio Takeuchi, Joan W Miller, Demetrios G Vavvas; Inhibition of inflammasome rescues photoreceptor cell death after retinal detachment.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1734.
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© ARVO (1962-2015); The Authors (2016-present)
Damage-associated molecular patterns (DAMPs) are released from dead cells and activate molecular platforms containing caspase-1, termed ‘inflammasome’, which lead to the release of mature IL-1β in monocytes/macrophages. Meanwhile, IL-1β is known to activate inflammatory responses and lead to cell death. In this study, we investigated whether inflammasome was activated in the mice eyes after retinal detachment (RD). Furthermore, we examined whether inhibition of inflammasome could reduced photoreceptor cell death after RD.
RD was induced in mice eyes, by injection of 4 ul of sodium hyaluronate into the subretinal space of C57/BL6 mice. Caspase 1 inhibitor, Ac-Tyr-Val-Ala-Asp-Chloromethylketone (YVAD), was diluted with sodium hyaluronate to a final concentration of 300 μM. The levels of total IL-1β and cleaved IL-1β after RD in mice eyes were measured with ELISA and western blotting respectively. To evaluate the quantity of cell death, collected eyes were frozen in O.C.T Compound and cut into 8 μm thick-section. TUNEL staining was performed with ApopTag Fluorescein In Situ Apoptosis Detection Kit.
Total IL-1β including pro- IL-1β and cleaved IL-1β increased as early as 6 hours after the induction of RD, peaked at 12 hours (6.3 fold compared to control) and was down-regulated after 24 hours. Cleaved IL-1β peaked at 24 hours after RD simultaneously with the peak of TUNEL positive cells in outer nuclear layer. Treatment with the Caspase1 inhibitor YVAD decreased cell death by 55.3%.
Retinal detachment induced inflammasome activation in mice eyes. Inhibition of inflammasome significantly reduced photoreceptor cell death after RD suggesting potential novel neuroprotective strategies.
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