Comparison of mouse models of dry eye syndrome

Objective: In order to compare the characteristics of two mouse models of dry eye disease (DES) established by scopolamine hydrobromide (SCOP) and atropine sulfate (ATPS). Additionally, the effect of paeoniflorin (PF) was evaluated to verify the reliability of models. Methods: Following adaptive feeding, C57BL/6J mice were randomly assigned to five groups: Normal Control (NC), SCOP model, SCOP+PF, ATPS model, and ATPS+PF. The SCOP group mice were subcutaneously injected with 2.5 mg/mL SCOP solution at 25 mg/kg (0.2 mL each time, twice daily at 10:00 and 16:00) into the nape of the neck. For the ATPS group, 1% ATPS ophthalmic gel (5 μl each time, three times daily at 10:00, 13:00, and 16:00) was administered as local eye drops. Mice in the SCOP+PF and ATPS+PF groups were administered a 1% PF solution (5 μl each time, three times a day) 15 min after modeling for 14 days, respectively. General health and ocular changes in the mice were observed throughout the study. The Schirmer Test (SIT), Tear Film Breakup Time (BUT), Corneal Fluorescein Staining Score (FLS), and Tear Ferning Test (TFT) were conducted at 7 and 14 days. Two staining techniques were used to evaluate the characteristics of the two DES models: Hematoxylin-eosin (HE) staining was used to examine the morphology of corneal and lacrimal gland tissues, while periodic acid-Schiff (PAS) staining assessed the number of goblet cells in the conjunctiva. Results: General observation showed that mice in SCOP group were agitated and irritable, with significantly increased activity, and exhibiting increased water intake and slight weight loss. In contrast, the ATPS group presented no significant changes in general condition but began to present secretions from the ocular surface from day 3. The ophthalmologic evaluation showed a significantly insufficient tear secretion in SCOP group, which worsened with the time of manufacture of the model. Regarding changes in BUT and FLS, symptoms were more severe in ATPS group than in SCOP group on the 7 th day of the experiment, while the opposite occurred on day 14. The fern-like substances in tear crystallization in both model groups significantly decreased. Histopathological examinations of the ocular accessory tissues revealed significant damage to the lacrimal gland in the SCOP group, along with disordered corneal morphology and reduced conjunctival goblet cells in the ATPS group. Treatment of PF was effective in improving tear secretion, stabilizing the tear film homeostasis and restoring corneal injury in both SCOP and ATPS models. Conclusion: Both models induced relatively mild dry eye symptoms. The SCOP modeling method, which inhibits parasympathetic nerve excitation to reduce tear and mucin secretion, is characterized by decreased tear secretion, a slow onset, and long-lasting effects, making it suitable for establishing long-term mild to moderate dry eye syndrome. In contrast, the ATPS modeling method primarily induces ocular surface damage, has a rapid onset, and shows compensatory recovery after one week, making it suitable for short-term mild DES. Both methods are applicable for the study of the early pathogenesis of tear-deficient DES, as well as its prevention and treatment.