July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The NLRP3 Inflammasome is Involved in the Pathogenesis of Experimental Murine Cytomegalovirus (MCMV) Retinitis in Mice with Retrovirus-induced Immunosuppression (MAIDS)
Author Affiliations & Notes
  • Jessica Carter
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Jay Oh
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Lauren Duncan
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Madeline Welch
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Max Housman
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Richard D Dix
    Biology, Georgia State University, Atlanta, Georgia, United States
    Ophthalmology, Emory University, Atlanta , Georgia, United States
  • Footnotes
    Commercial Relationships   Jessica Carter, None; Jay Oh, None; Lauren Duncan, None; Madeline Welch, None; Max Housman, None; Richard Dix, None
  • Footnotes
    Support  NIH Grant EY010568, NIH Grant EY024630, NIH/NEI Core Grant P30/EY006360, Emory Eye Center Vision Training Grant NIH/NEI T32EY007092, Research to Prevent Blindness, and Fight for Sight
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 517. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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