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Ronan Cunning, Sofia Pavlou, Alan W Stitt, Heping Xu, Mei Chen; Inflammasome activation in the photoreceptor cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2730. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor death is the ultimate cause of vision loss in various retinal disorders, including age-related macular degeneration (AMD) and uveoretinitis. Inflammasomes are the key signalling platforms that detect pathogenic microorganisms and sterile stressors and activate the highly pro-inflammatory cytotoxic cytokines interleukin (IL)-1b and IL-18. In this study, we investigated the role of inflammasome activation in photoreceptor death.
The expression of inflammasome components including NLRP1, NLRP3, AIM2, ACS, caspase 1, and caspase 11 by the mouse photoreceptor cell line 661W under clinical relevant stimulations including TNFα, IFNg, cytosolic DNA, and high glucose (25mM) were investigated using Western blotting and qRT-PCR. The production of IL-1b and IL-18 in the supernatants was measured by ELISA. Cell viability was assessed using the LDH (Lactate dehydrogenase) cytotoxicity assay. T-test was used for statistical analysis.
Under normal culture conditions, photoreceptor cells (661W) express low levels of NLPR3, AIM2, and caspase 1. The expression levels of AIM2 (p-value <0.001) and NLRP3 (p-value <0.001) were increased following TNFa and cytosolic DNA treatment. The treatment also induced IL-18 (p-value <0.001) expression and cell death. High glucose treatment (72h) did not induce inflammasome activation in 661W cells and the viability of the cells was also not affected by the treatment.
Inflammasome activation and cell death can be induced in photoreceptor cells under inflammatory conditions. Our results suggest that inflammasome activation may play an important role in photoreceptor damage under disease conditions including age-related macular degeneration and uveoretinitis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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