Investigating the Role of Autonomic Dysfunction in the Pathogenesis of Depression-Related Dry Eye.

PURPOSE: This study aimed to investigate the functional and pathological changes in the lacrimal gland (LG) of depression-related dry eye (DE), as well as the role of autonomic nerves in this process. METHODS: The chronic unpredictable mild stress (CUMS) models were established to induce depression. The depression-like behaviors were evaluated by behavioral tests. DE indicators were detected by corneal fluorescein staining, tear film breakup time, and tear secretion. The systemic and lacrimal autonomic nerves were evaluated by heart rate variability (HRV), ELISA, immunofluorescence staining, and Western blot. The tissue and molecular assays were performed to assess the levels of inflammation, oxidative stress, and apoptosis in the LG. After modeling, 6-hydroxydopamine (6-OHDA) was given to inhibit sympathetic nerves, the changes of DE indicators and LG pathological damage were further observed by repeating the above tests. RESULTS: CUMS could induce depressive-like behaviors while inducing DE, which is manifested by decreased tear secretion and increased corneal staining. Meanwhile, CUMS could induce autonomic dysfunction, especially sympathetic nerve activation, resulting in organizational structure disorders, decreased expression of α-SMA, and elevated reactive oxygen species (ROS) levels and apoptosis in the LG. Sympathetic denervation could improve DE indicators, reduce ROS and apoptosis of the LG, and improve the drainage function of the LG. CONCLUSIONS: During the development of depression, CUMS can also cause functional and pathological damages to the LG by activating sympathetic nerves to induce depression-related DE. TRANSLATIONAL RELEVANCE: This suggests that intervention measures targeting autonomic dysfunction may be a new direction for the treatment of depression-related DE.