Chronic sleep deprivation promotes experimental autoimmune uveitis through STAT1 phosphorylation, ISG15 expression and enhanced pathogenicity of macrophages

Autoimmune uveitis (AU) is a severe intraocular inflammatory disease driven by dysregulated T-cell immunity and macrophage activation, leading to retinal tissue damage. Experimental autoimmune uveitis (EAU), an animal model, closely mimics human AU, highlighting the role of macrophages in inflammation and immune regulation. Chronic sleep deprivation (CSD), caused by prolonged circadian rhythm disruption, further exacerbates immune dysfunction by activating microglia and enhancing inflammation. This study investigates the combined impact of EAU and CSD on retinal transcriptomics, focusing on immune and inflammatory pathways, providing insights into the interaction between circadian rhythm disruptions and autoimmune uveitis progression. Heathy B10.RIII mices rep1, rep2, rep3;Chronic sleep deprivation treatment of healthy B10.RIII mice for 4 weeks;Treatment of B10.RIII mice using IRBP peptide emulsified 1:1 with complete Freund's adjuvant (CFA) containing inactivated Mycobacterium tuberculosis for 2 weeks rep1, rep2, rep3;Treatment of B10.RIII mices using IRBP peptide emulsified 1:1 with CFA containing inactivated Mycobacterium tuberculosis for an additional 2 weeks, followed with chronic sleep deprivation for 4 week rep1, rep2, rep3: