June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
IL-1α is Stimulated Intraocularly in Mice with Retrovirus-Induced Immunosuppression (MAIDS) During Development of Experimental Murine Cytomegalovirus (MCMV) Retinitis
Author Affiliations & Notes
  • Shauntelle Byfield
    Georgia State University, Atlanta, Georgia, United States
  • Gisseth A. Mora Scarpetta
    Georgia State University, Atlanta, Georgia, United States
  • Jessica Carter
    Georgia State University, Atlanta, Georgia, United States
    Emory University, Atlanta, Georgia, United States
  • Jay Oh
    Georgia State University, Atlanta, Georgia, United States
  • Judee Grace Nemeño
    Georgia State University, Atlanta, Georgia, United States
  • Richard D Dix
    Georgia State University, Atlanta, Georgia, United States
    Emory University, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Shauntelle Byfield, None; Gisseth Mora Scarpetta, None; Jessica Carter, None; Jay Oh, None; Judee Grace Nemeño, 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 2020, Vol.61, 436. doi:
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    • Get Citation

      Shauntelle Byfield, Gisseth A. Mora Scarpetta, Jessica Carter, Jay Oh, Judee Grace Nemeño, Richard D Dix; IL-1α is Stimulated Intraocularly in Mice with Retrovirus-Induced Immunosuppression (MAIDS) During Development of Experimental Murine Cytomegalovirus (MCMV) Retinitis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):436.

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

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Abstract

Purpose : IL-1α is a unique cytokine that serves as an alarmin to signal cell injury and induce innate immunity via macrophage activation. Because macrophages are prominent in the pathogenesis of MAIDS-related MCMV retinitis, we tested the hypothesis that IL-1a is stimulated within MCMV-infected eyes of mice with MAIDS during retinitis progression. Both precursor and mature forms of IL-1a were included in the study because both forms are biologically active.

Methods : The left eyes of retinitis-susceptible mice with 10-week MAIDS (MAIDS-10 mice) and retinitis-resistant mice with 4-week MAIDS (MAIDS-4 mice) were injected subretinally with MCMV. The right eyes of both animal groups were mock infected with maintenance medium only (controls). MCMV-infected and mock-infected eyes were collected from both groups at 3, 6, and 10 days after injection and compared for amounts of precursor IL-1a mRNA by quantitative real-time RT-PCR assay and for precursor and mature IL-1a protein by western blot analysis.

Results : Compared with mock-infected eyes, MCMV-infected eyes of MAIDS-4 and MAIDS-10 mice showed significant production of precursor IL-1a mRNA at 3 days postinfection (dpi), but levels of precursor mRNA were remarkably ~7 times higher within retinitis-susceptible eyes when compared with retinitis-resistant eyes. Intraocular levels of precursor IL-1a mRNA subsequently decreased within MCMV-infected eyes of both groups at 6 and 10 dpi. Whereas no difference was observed at 6 dpi for precursor IL-1a protein amounts within mock-infected and MCMV-infected eyes of MAIDS-4 mice, MCMV-infected eyes of MAIDS-10 mice showed elevated amounts of precursor IL-1a precursor protein when compared with mock-infected eyes at all times tested. In contrast, no substantial difference was observed in amounts of mature IL-1a protein within mock-infected and MCMV-infected eyes of MAIDS-10 mice.

Conclusions : Our findings provide new evidence that IL-1a is stimulated intraocularly during development of MAIDS-related MCMV retinitis, but surprisingly suggest that precursor IL-1a is more involved than mature IL-1a in retinal disease pathogenesis. High amounts of intraocular infectious virus and/or a needlestick inflammatory response could account for detectable amounts of IL-1a mRNAs and proteins within MCMV-infected eyes of MAIDS-4 mice without retinitis.

This is a 2020 ARVO Annual Meeting abstract.

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