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Updated: Apr 19, 2026

A Chronic Autoimmune Dry Eye Rat Model with Increase in Effector Memory T Cells in Eyeball Tissue
Published on: June 7, 2017
Depression induces ocular surface inflammation and dry eye-like changes in mice
Xiang Lin1, Yu-Wen Liu2, Jia-Ni Li2
1Department of Ophthalmology, Xiang'an Hospital of Xiamen University; Eye Institute of Xiamen University; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Fujian Engineering and Research Center of Eye Regenerative Medicine; School of Medicine, Xiamen University, Xiamen 361005, Fujian Province, China.
Aim:
To investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model, with a focus on dry eye-like alterations.
Methods:
Male C57BL/6J mice (10-12 weeks old) were randomly assigned to control or restraint stress (RS) groups. The RS group underwent three intermittent 24-hour restraint sessions to induce depressive-like behavior. Behavioral testing, tear secretion measurement, and corneal Oregon Green Dextran (OGD) staining were performed. Postmortem analyses included histological evaluation of lacrimal glands, goblet cell quantification using periodic acid-Schiff staining, and assessment of key inflammatory and apoptotic markers: interleukin (IL)-17, matrix metalloproteinases (MMP)-3, MMP-9, IL-13, interferon (IFN)-γ, and cleaved caspase-3 and -8.
Results:
Repeated RS induced depression-like behavior and significant ocular surface changes. RS-treated mice showed increased corneal OGD uptake and upregulation of gene/protein expression of IL-17, MMP-3, and MMP-9 (P<0.05). Goblet cell density and IL-13 protein expression were reduced, while IFN-γ protein expression was elevated (P<0.05). Cleaved caspase-3 and -8 levels were significantly increased in both cornea and conjunctiva. Tear volume and lacrimal gland size were unchanged; however, mild inflammatory infiltration was observed in lacrimal glands.
Conclusion:
Repeated RS leads to ocular surface inflammation and dry eye-like pathology, including corneal barrier disruption, goblet cell loss, and epithelial apoptosis. These findings suggest that depression contributes to the pathogenesis of dry eye disease via immune-mediated mechanisms.

