Validation of a preclinical dry eye model in New Zealand white rabbits during and following topical instillation of 1% ophthalmic atropine sulfate

Abstract

Abstract Background The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate (OAS) in New Zealand white (NZW) rabbits. Methods OAS (1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21, and 30 (OAS group). A second group (n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were: Schirmer I test, tear break‐up time (TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated. Results While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control (p < 0.001), and versus basal production (p < 0.001). TBUT showed statistically significant differences between groups (days 3 and 10; p = 0.001) and versus basal values (day 3; p < 0.001). Fluorescein staining showed a statistically significant difference (day 3; p = 0.001). The most frequent clinical finding was conjunctival hyperemia (76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation (86.7% minimal; 13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference. Conclusions The effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention; it is not a viable model after OAS administration is suspended.

Keywords

• atropine sulfate
• dry eye
• rabbit model
• safety
• Schirmer I test
• TBUT