Diurnal rhythm-modulated transcriptome analysis of meibomian gland in hyperlipidemic mice using RNA sequencing.

Aim: To explore the regulatory mechanism of meibomian gland (MG) in hyperlipidemic mice under a diurnal rhythm by transcriptomic analysis based on high-throughput sequencing.

Methods: The mouse model of hyperlipidemia induced by four months of high-fat diet (HFD) feeding to a regular light-dark (LD) cycle for 2 weeks was used in this study. Phenotypic observation and RNA sequencing (RNA-seq) of MGs of the experimental mice were then performed to investigate transcriptional changes due to hyperlipidemia and the diurnal rhythm and their effects on meibomian gland dysfunction (MGD).

Results: The expression levels of the identified dysregulated genes were then validated by qRT-PCR. Several significantly regulated genes and enriched pathways were identified as associated with MGD in hyperlipidemic mice under a diurnal rhythm; these genes included some core diurnal clock genes, e.g., Clock, Per2 and Per3. Phenotypic and histological analysis reveals abnormal morphology concomitantly with a modification of the transcriptional landscape of MG caused by HFD.

Conclusion: Our findings provide us with a deeper understanding of the diurnal rhythm regulation of MG in hyperlipidemic mice altered by daily nutritional challenge.