Purpose: The aim of this study was to establish a clinically relevant short-term animal model
of dry eye with utility in identifying compounds with potential therapeutic efficacy.
Methods: Rabbit lacrimal glands were injected with the T-cell mitogen Concanavalin A
(Con A) and inflammation, tear function, and corneal epithelial cell integrity were subsequently
assessed. The inflammatory response was characterized by quantifying biochemical
markers of inflammation ex vivo and by confirming inflammatory cell influx by histology.
Matrix metalloproteinase-9 (MMP-9) and proinflammatory cytokines IL-1β, IL-8, and TGF-β1
were quantified in tissue extracts. Tear function was monitored by measuring tear fluorescein
clearance and tear breakup time (TBUT). Corneal epithelial cell integrity was determined
by quantifying the uptake of methylene blue dye following the exposure of rabbits to a lowhumidity
environment. The anti-inflammatory corticosteroid, dexamethasone, was administered
topically as indicated for each study.
Results: Histopathologic evaluation of lacrimal glands injected with Con A revealed a pronounced
inflammatory process characterized by lymphocytic infiltration, multifocal necrosis,
and fibroplasia. Elevated levels of MMP-9 and cytokines IL-1β, IL-8, and TGF-β1 were detected
in the lacrimal gland and cornea. Inflammation of the rabbit lacrimal gland following
an injection of Con A significantly reduced tear clearance and TBUT and increased susceptibility
to desiccation-induced corneal damage. Dexamethasone was prophylactically and therapeutically
effective in this inflammation model of dry eye, restoring tear function and inhibiting
corneal injury following topical ocular application.
Conclusions: Characteristics of this rabbit lacrimal gland inflammation model of dry eye
are consistent with the current understanding of dry eye as a local ocular surface inflammatory
response to abnormal tear volume and composition. These results suggest that this rabbit
model of dry eye may be employed to assess the therapeutic efficacy of mechanistically
diverse agents on clinically relevant signs of ocular surface disease. These methods were
strategically developed to be applicable for advancing drug discovery for a broad spectrum
of dry eye patients.
