A murine model of dry eye induced by an intelligently controlled environmental system

To establish a novel murine model of dry eye using an intelligently controlled environmental system (ICES).

Thirty BALB/c mice aged 4 to 6 weeks were housed in the ICES in which the relative humidity, airflow, and temperature were maintained at 15.3% +/- 3% (mean +/- SD), 2.1 +/- 0.2 m/s, and 21 degrees to 23 degrees C, respectively, for 42 days. Thirty mice of similar age and housed in a normal environment were controls (relative humidity, 60%-80%; no airflow; temperature, 21 degrees -23 degrees C). The ocular surfaces of the animals in both groups were analyzed before and 3, 7, 14, 28, and 42 days after the experiment for aqueous tear production, corneal barrier function, conjunctival morphology, and goblet cell density. The level of apoptosis on the ocular surface also was assessed using active caspase-3 at 42 days.

A low-humidity environment was maintained constantly by the ICES. Animals in this environment had decreased aqueous tear production, increased corneal fluorescein staining, and marked thinning and accelerated desquamation of the apical corneal epithelium compared with control eyes. Squamous metaplasia of the conjunctival epithelium with decreased goblet cell density also developed in the animals housed in the ICES. Active caspase-3 was highly expressed on the ocular surfaces of the animals housed in the ICES at 42 days.

The biological and morphologic changes of dry eye induced by ICES in mice are similar to those in humans. This dry eye environment appears to upregulate apoptosis on the ocular surface.