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Laura Belen, Kortni Violette, George W Ousler, Andy Whitlock; Optimization of an Inflammation-Based Murine Model of Dry Eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3663.
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Several approaches are currently used to model dry eye disease in mice; most of these involve reducing or eliminating lacrimal gland function without inducing inflammation. A limitation of such models is their inability to assess drugs that alleviate dry eye symptomology by reducing inflammation. The T-cell mitogen Concanavalin A (ConA) has been previously utilized in a rabbit model of dry eye to study the potential of anti-inflammatory drugs (Nagelhout 2005). In this study, we optimized this ConA model in mice to create a modifiable inflammatory dry eye model.
Eyes of 10-12 week old female C57 mice were evaluated at baseline by corneal fluorescein staining and tear measurement with phenol red threads (ZoneQuick®). Animals were randomized based on their staining and tear volumes so that each group had a normalized baseline response. Mice were injected in the lacrimal gland with 100, 50, or 10µg/10µL of ConA or 10µL of phosphate buffered saline (PBS). An additional group of mice were treated with subcutaneous scopolamine and served as a positive control. For all studies, animals were placed in Ora’s controlled adverse environment (CAE) and were followed for 24 to 72 hours post-injection for corneal staining and tear measurement.
ConA-injected mice showed a significant (p <.05), dose-dependent increase in corneal staining 24 hours post-injection when compared to the PBS-injected mice. Staining scores were 11.2, 7.0, 3.3 and 2.9, respectively, for the 100µg-, 50µg-, 10µg-, and 0µg-ConA injected animals. Staining declined from 24 to 48 hours, and returned to baseline for all groups by 72 hours. All ConA-injected mice showed a significant (p <.05) decrease in tear volume at 24 hours post-injection as compared to PBS-injected mice; these decreases returned to control values by 72 hours post-injection, and were not dose-dependent.
Our study shows that ConA injection can evoke an inflammatory reaction in the lacrimal gland leading to increases corneal staining and reduction in tear production. Interestingly, the effect on corneal staining is independent of the extent of tear gland suppression, and more dependent on the degree of inflammation. Our study establishes that ConA-induced inflammation in mice, in conjunction with CAE, can produce an acute form of dry eye disease that is modifiable and applicable for studying novel dry eye drugs.
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