Abstract
Purpose :
Diabetes-related dry eye is one of the ocular surface complications associated with diabetes mellitus (DM). Recent studies have revealed that Glucagon-like peptide 1 (GLP-1) interacts with the GLP-1 receptor (GLP-1R) and contributes to alleviating abnormal oxidative stress, inhibiting levels of oxidative stress and inflammation, thereby playing a protective role in diabetic complications. This study was to evaluate the efficacy of topical GLP-1 agonists (GLP-1 RA) liraglutide in alleviating lacrimal gland inflammation in a murine model of diabetes-associated dry eye.
Methods :
The type 1 diabetes murine model was established by injection of streptozotocin intraperitoneally. The liraglutide eye drops were administered five times daily for seven days, commencing three months after the establishment of the murine model of diabetes. A saline solution was used as the control group. Tear secretion was evaluated using phenol red threads. Lacrimal glands were isolated for histological analysis to evaluate the degree of lacrimal gland damage. RNA-sequencing (RNA-Seq) was used to explore the pathogenesis of hyperglycemia-induced lacrimal gland injuries. Primary lacrimal epithelial cells of mice were isolated and cultured in high glucose (HG) medium to further investigate potential mechanisms. The DCFH-DA assay was applied to measure the production of reactive oxygen species (ROS).
Results :
First, we ascertained the expression of GLP-1R in the lacrimal gland and observed a diabetes-induced down-regulation of GLP-1R. Moreover, RNA-seq data from lacrimal gland tissues revealed that the differentially expressed genes (DEGs) were enriched in the inflammatory response pathway. Histological analysis demonstrated that persistent hyperglycemia induced infiltration of inflammatory cells and progressive fibrosis in the lacrimal gland acini, resulting in diminished tear secretion. Topical application of liraglutide effectively attenuated immune cell infiltration, alleviated lacrimal gland fibrosis, and promoted tear production in diabetic mice. The DCFH-DA assay revealed that liraglutide administration mitigated ROS production induced by HG in primary lacrimal epithelial cells.
Conclusions :
Our findings demonstrated that topical liraglutide eye drops could alleviate hyperglycemia-induced oxidative damage in the lacrimal gland and increase tear secretion.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.