Abstract
Purpose :
The lacrimal gland (LG) is critical for maintaining the homeostasis of the ocular surface microenvironment through secreting aqueous tear in mammals. Many systemic metabolic diseases can alter the lacrimal gland function. This study aims to explore the effect of hyperuricemia (HUA) on LG in a mouse model.
Methods :
Male C57BL/6 mice were orally administrated of yeast polysaccharide combined with intraperitoneal injection of potassium oxonate to establish a HUA animal model. Corneal fluorescence staining of mice was observed by slit-lamp microscopy. Tear production was evaluated by phenol red thread and tears were collected with capillary pipette at different time points. Protein in tear was detected by Western blot assay. Tear and serum uric acid were measured by uric acid assay kit. LGs were harvested for H&E staining, Masson staining, qRT-PCR, Western blot assay, immunofluorescence staining (IF staining) and TUNEL assay. Eye tissues were collected and processed for H&E staining and IF staining.
Results :
The serum uric acid levels in the HUA mice increased at week 2 and remained stable until week 6. HUA induced obvious ocular surface changes, including decreased tear production, corneal epithelial defects, and squamous metaplasia of the corneal epithelia. Uric acid was detected in the tears of HUA mice and the inflammatory cytokines TNF-α, IL-1β, and IL-6 increased in the tears of HUA mice. Inflammatory cell infiltration with increased expression of inflammatory factors was found in LG of HUA mice. Meanwhile, HUA mice exhibited downregulation of α-SMA, AQP5 and Ki67 expression and upregulated cell apoptosis in LGs. Masson staining showed LG fibrosis after 4 weeks of HUA modeling. Serum uric acid levels reduced after 8 weeks of modeling, while the structural and functional changes of the LGs did not recover.
Conclusions :
HUA could induce inflammation, fibrosis, cell apoptosis and proliferation inhibition in LG, resulted in aqueous tear deficient dry eye in mouse model.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.