STAT3 Mediated Inflammation is Involved in Diabetes Mellitus-Related Dry Eye in Rats

Abstract

Background: Dry eye is an ocular complication of diabetes mellitus. Due to its complex pathogenesis, treatment still needs to be studied. Objectives: This study aimed to explore the role of signal transducer and activator of transcription 3 (STAT3) in diabetes mellitus-related dry eye. Methods: High-fat and high-carbohydrate diet and streptozotocin were used to establish a diabetes mellitus-related dry eye rat model. All rats were divided into four groups (n = 6 in each group), including control group, diabetes mellitus-related dry eye group (model group), vehicle group, and STAT3 inhibitor group (S3I-201 group). Tear production was assessed using phenol red cotton threads. A CochetBonnet esthesiometer was used to evaluate corneal sensitivity. Periodic acid-schiff (PAS) and in situ terminal deoxynucleotidyl transferase (TUNEL) staining were conducted to measure the number of goblet cells and apoptotic cells in conjunctivae. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the levels of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-17A (IL-17A), and Interleukin-1β (IL-1β) in the conjunctival tissues. Western blot was applied for assessing the expression of nuclear factor-κB (NF-κB)/STAT3 pathway related proteins. Results: S3I-201 increased tear production, corneal sensitivity, the number of goblet cells, and decreased cell apoptosis in diabetes mellitus-related dry eye rats (p < 0.05). Moreover, diabetes mellitus-related dry eye has the potential to induce inflammation by upregulating the levels of TNF-α, IL-6, IL-17A, and IL-1β (p < 0.05), which were significantly reduced after S3I-201 treatment (p < 0.05). In addition, diabetes mellitus-related dry eye induced activation of NF-κB pathway and increased the ratio of p-STAT3/STAT3, both of which were reversed by S3I-201 treatment (p < 0.05). Conclusions: Inhibition of STAT3 alleviated diabetes mellitus-related dry eye in rats by regulating the inflammation.