June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Pyroptosis Inducer, Gasdermin D, is Stimulated Intraocularly in Mice with Retrovirus-Induced Immunosuppression (MAIDS) During Experimental Murine Cytomegalovirus (MCMV) Retinitis
Author Affiliations & Notes
  • Jessica Carter
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Quentin Richardson
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Gabriela Jasso
    Biology, Georgia State University, Atlanta, Georgia, United States
  • Christine Alston
    Biology, Georgia State University, Atlanta, Georgia, United States
    Emory University, Decatur , Georgia, United States
  • Richard D Dix
    Emory University, Decatur , Georgia, United States
  • Footnotes
    Commercial Relationships   Jessica Carter, None; Quentin Richardson, None; Gabriela Jasso, None; Christine Alston, 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 June 2017, Vol.58, 3626. doi:
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      Jessica Carter, Quentin Richardson, Gabriela Jasso, Christine Alston, Richard D Dix; Pyroptosis Inducer, Gasdermin D, is Stimulated Intraocularly in Mice with Retrovirus-Induced Immunosuppression (MAIDS) During Experimental Murine Cytomegalovirus (MCMV) Retinitis
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):3626.

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

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Abstract

Purpose : Pyroptosis is a cell death pathway whose potential contributions to retinal disease remain unexplored. We have shown previously that key pyroptosis-related molecules caspase-1, interleukin-1β (IL-1β), and IL-18 mRNAs are stimulated within MCMV-infected eyes during the progression of retinitis in mice with MAIDS [J Virol, 2012]. To determine the mechanism(s) by which MCMV might stimulate pyroptosis, we performed a series of in vivo studies to test the hypothesis that mRNA for gasdermin D (GSDMD), a recently discovered molecule that is critical for release of IL-1β during pyroptosis, is stimulated during the pathogenesis of MAIDS-related MCMV retinitis.

Methods : Groups of retinitis-sensitive mice with MAIDS (n = 3 – 5) were injected subretinally with MCMV (left eyes) or maintenance medium only (right eyes). MCMV-infected and control eyes were harvested at 6 and 10 days after subretinal injection and assessed for GSDMD mRNA by quantitative real-time RT-PCR assay. Results: As expected, MCMV-infected eyes of retinitis-susceptible mice with MAIDS showed marked stimulation of IL-1β mRNA production when compared with uninfected control eyes that peaked at day 6 after subretinal MCMV inoculation. In comparison, MCMV-infected eyes of retinitis-susceptible mice with MAIDS showed a modest yet significant stimulation of GSDMD mRNA at days 6 and 10 after subretinal MCMV inoculation.

Results : As expected, MCMV-infected eyes of retinitis-susceptible mice with MAIDS showed marked stimulation of IL-1β mRNA production when compared with uninfected control eyes that peaked at day 6 after subretinal MCMV inoculation. In comparison, MCMV-infected eyes of retinitis-susceptible mice with MAIDS showed a modest yet significant stimulation of GSDMD mRNA at days 6 and 10 after subretinal MCMV inoculation.

Conclusions : That MCMV-infected eyes of retinitis-sensitive mice with MAIDS showed stimulation of GSDMD mRNA production concomitant with stimulation of IL-1β mRNA production further supports a role for pyroptosis in the pathogenesis of MAIDS-related MCMV retinitis and agrees with recent findings that GSDMD production is related to release of the pyroptosis-related molecule IL-1β. Studies are underway to determine if IL-1β mRNA stimulation is dependent or independent of caspase-1 and/or caspase-11.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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