@article{Lin2026, 
author = {Xiang Lin and Yu-Wen Liu and Jia-Ni Li and Wei-Jie Ouyang and Li-Ying Tang and Jie-Li Wu and Zhao-Lin Liu and Shi-Nan Wu and Jiao-Yue Hu and Zu-Guo Liu},
title = {Depression induces ocular surface inflammation and dry eye-like changes in mice},
year = {2026},
journal = {International Journal of Ophthalmology},
volume = {19},
number = {3},
pages = {434-442},
keywords = {depression, restraint stress, dry eye, ocular surface damage, inflammation, mice},
url = {https://www.sciopen.com/article/10.18240/ijo.2026.03.02},
doi = {10.18240/ijo.2026.03.02},
abstract = {AIMTo investigate the impact of depression-like behavior on ocular surface homeostasis in a mouse model, with a focus on dry eye-like alterations.METHODSMale 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.RESULTSRepeated 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.CONCLUSIONRepeated 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.}
}