Exposure to a Dry Environment Induces Strain–Specific Dry Eye in Mice

Abstract

Abstract: : Purpose: Most current dry eye animal models have a single causative mechanism, and do not take into consideration the influence of environmental conditions on tear secretion and ocular surface signs. The purpose of the present study was to test the hypothesis that strains with specifically biased T cell responses develop differential signs of dry eye when exposed to a low humidity setting. Methods: Eight to12–week–old BALB/c (T helper–2 biased) and C57BL/6 (T helper–1 biased) mice were placed in our controlled environment chamber (CEC) where relative humidity (RH), temperature (T), and air flow (AF) are regulated and monitored. Mice were exposed to specific environmental controlled conditions (RH = 21.7 ± 5.2%, AF = 15 l/min, T = 21–23°C) for 3 and 7 days. Control mice were kept in a normal environment (RH = 50–70%, no AF, T = 21–23°C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score 0–15), goblet cell density in the superior and inferior conjunctiva, and corneal epithelial thickness in histologic sections were measured by a masked observer. Results: No statistically significant differences between the groups were found at baseline. Statistically significant decreases in tear secretion were seen after exposure to the CEC environment. Mean cotton thread wetting was respectively 1.8, 1.4, and 0.9 mm for control, BALB/c, and C57BL/6 at day 3, and 1.7, 0.9, and 0.4 mm for control, BALB/c, and C57BL/6 mice at day 7. C57BL/6 mice showed reduced tear secretion as compared to BALB/c at each time point (P<.005, t test). BALB/c and C57BL/6 mice showed a significant increase in corneal fluorescein staining and epithelial thickness at day 3 and 7 as compared to controls. Goblet cell density was significantly decreased in the superior and inferior conjunctiva in the BALB/c at day 7, and even earlier (day 3) in C57BL/6 mice. Conclusions: This study indicates that exposure of non–pharmacologically modified normal mice to a low humidity environment in the CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye–related ocular surface signs which appear to be strain–specific, and more significant in T helper–1 biased C57BL/6 mice.

Keywords: cornea: tears/tear film/dry eye • anterior segment • lacrimal gland