Light cycle phase advance as a model for jet lag reprograms the circadian rhythms of murine extraorbital lacrimal glands.

Abstract Purpose Jet lag causes a disruption in physiological rhythms in humans. This study aims to explore the extent to which jet lag affects the circadian rhythmicity in the lacrimal glands. Methods C57BL/6J mice were subjected to a 12-h light/12-h dark (LD) cycle and an 8-h advanced LD schedule as a model for jet lag. On day 5 after the LD advance, the extraorbital lacrimal glands (ELGs) were collected at 3-h intervals during a 24-h cycle. Total mRNA was extracted from normal and advanced LD-treated ELGs and assayed using high-throughput RNA sequencing. The rhythmic transcripts were identified, analyzed, and visualized by bioinformatics techniques. Finally, (i) animal behavior; (ii) the mass, cell size, and secretion response of ELGs; and (iii) circadian migration of immune cells to ELGs were also assayed. Results Jet lag treatment drastically altered the phase and composition of the rhythmic transcripts compared to that of normal ELGs. The key biological processes, signaling pathways, and protein–protein association networks were also dramatically altered in a spatiotemporal pattern. Furthermore, the circadian migration of neutrophils, T cells, B cells, and macrophages to the ELGs increased and shifted later by 6-h. Finally, the circadian rhythms of the ELGs with respect to mass, cell size, and secretion response were also impaired in jet lag-treated animals. Conclusions Jet lag impairs the circadian rhythm of the transcriptomic profile, structure, and secretion function of the lacrimal glands. This information provides novel insight into the negative effects of jet lag on ELGs.