Abstract

The lacrimal gland is critical for maintaining the homeostasis of the ocular surface microenvironment through secreting aqueous tears in mammals. Many systemic diseases such as Sjögren's syndrome, rheumatoid arthritis and diabetes can alter the lacrimal gland function, eventually resulting in aqueous tear deficient dry eye. Here, we used a high fat diet (HFD) experimental mouse model to clarify how hyperlipidemia affects lacrimal gland function. Aqueous tear secretion fell about 50% after 1 month on a HFD. Lipid droplets accumulated in the matrix and acinar cells of the lacrimal gland after this period, along with changes in the lipid metabolism, gene expression levels and disruption of fatty acid oxidative activity. Immune cell infiltration and rises in the gene expression levels of inflammation related cytokines: IL1β, TNFα, TSG6, IL10, MMP2, and MMP9 were found HFD also induced mitochondrial hypermegasoma, increased apoptosis and decreased lacrimal gland acinar cell proliferation. Replacement of the HFD with the standard diet partially reversed pathological changes in the lacrimal gland. Similarly, supplementing the HFD with fenofibrate also partially reversed inhibited tear secretion and reduced lipid accumulation, inflammation and oxidative stress levels. We conclude that a HFD induces pathophysiological changes and functional decompensation of the lacrimal gland. Therefore, ingestion of a HFD may be a causative factor of dry eye disease.