Abstract
Purpose: :
To develop a murine model of desiccating stress-induced chronic dry eye disease (DED) and compare the changes in clinical signs over time.
Methods: :
DED was induced in 7-week-old female C57BL/6 mice by exposure to desiccating stress in a controlled environment chamber (CEC, relative humidity below 25%, airflow of 15 L/min and a constant temperature of 21°C to23°C) along with subcutaneous 0.1 mL injections of 5 mg/mL scopolamine three times daily for 14 days. Thereafter, the mice were divided into two groups. One group (group A) continued receiving the same challenge as before for another 14 days, and the other group (group B) was challenged with CEC exposure alone (without scopolamine) for the same period. Clinical signs of corneal dryness were evaluated using corneal fluorescein staining (CFS) at different time points. Punctate staining was recorded in a masked fashion with the standard National Eye Institute grading system of 0 to 3 for each of the five areas of the cornea.
Results: :
All mice developed clinical dry eye during the first 14 days of induction, with a CFS score of 10.9±0.4 (mean±SEM) at day 14. Thereafter, animals in both groups A and B showed a steady disease progression until the end of observation (day 28). The CFS scores in group A were 13.0±0.3 at day 21 (p = 0.004 vs. day 14), and 14.2±0.2 at day 28 (p < 0.001 vs. day 14). Group B exhibited CFS scores of 11.3±1.0 at day 21 (p = 0.6 vs. day 14), and 12.9±0.7 at day 28 (p = 0.02 vs. day 14). However, no significant difference in clinical signs was observed between group A and group B at either day 21 or day 28.
Conclusions: :
A robust and chronic model of DED can be successfully established by combing CEC and scopolamine challenges for 14 days, and thereafter with CEC exposure alone without scopolamine injection. This model can be further used to investigate the pathogenesis of chronic DED as well as potential therapies.
Keywords: cornea: tears/tear film/dry eye • autoimmune disease • cornea: basic science