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Jessica Carter, Jay Oh, Lauren Duncan, Madeline Welch, Max Housman, Richard D Dix; The NLRP3 Inflammasome is Involved in the Pathogenesis of Experimental Murine Cytomegalovirus (MCMV) Retinitis in Mice with Retrovirus-induced Immunosuppression (MAIDS). Invest. Ophthalmol. Vis. Sci. 2018;59(9):517. doi: https://doi.org/.
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Inflammasomes are important components of innate immunity and have been shown to induce pyroptosis in cells by promoting the maturity of inflammatory cytokines interleukin-1β and interleukin-18. We have shown previously that mRNAs for the nucleotide-binding oligomerization domain-like receptors (NLR) family of inflammasomes are stimulated within MCMV-infected eyes during the progression of retinitis in mice with MAIDS [J Virol, 2012]. To begin to define with greater precision the relative roles of NLR inflammasomes during pathogenesis of MAIDS-related MCMV retinitis, we focused on the NLRP3 inflammasome and performed a series of in vivo studies to test the hypothesis that the NLRP3 inflammasome is involved in the development of retinal necrosis associated with MCMV retinitis in mice with MAIDS.
The eyes of groups of NLRP3 inflammasome knockout mice with MAIDS and wildtype C57BL/6 mice with MAIDS were injected subretinally with MCMV. MCMV-infected eyes were collected 10 days later and subjected to either histopathologic analysis to determine frequency and severity of retinitis or standard plaque assay for quantification of infectious MCMV.
MCMV-infected eyes of NLRP3 knockout mice with MAIDS showed marked reduction in the severity and frequency of retinitis when compared with MCMV-infected eyes of wildtype mice with MAIDS despite no significant difference in the amounts of intraocular virus.
That MCMV-infected eyes of NLRP3 knockout mice with MAIDS showed a marked reduction of frequency and severity of retinitis supports a role for NLRP3 inflammasomes in the pathogenesis of MAIDS-related MCMV retinitis. Studies are underway to determine if other NLR-subset inflammasomes are essential for the pathogenesis of MCMV retinitis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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