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.