Modulation of Integrin α4β1 (VLA-4) in Dry Eye Disease

Objective: To study the effect of topical application of very late antigen 4 (VLA-4) small-molecule antagonist (anti-VLA-4 sm) in a mouse model of dry eye disease. Methods: Anti-VLA-4 sm (or control vehicle) was applied topically to mice placed in a controlled-environment chamber. Corneal fluorescein staining and conjunctival T-cell enumeration were performed in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva. Results: Dry eye syndrome induced increased corneal fluorescein staining, corneal and conjunctival tumor necrosis factor alpha messenger RNA expression, and T-cell infiltration into the conjunctiva. Very late antigen 4 blockade significantly decreased corneal fluorescein staining compared with the untreated dry eye disease and control vehicle-treated groups (P<.001 and P=.02, respectively). In addition, VLA-4 blockade was associated with a significant decrease in conjunctival T-cell numbers (P<.001 vs control vehicle-treated group) and tumor necrosis factor-alpha transcript levels in the cornea (P=.04 vs control vehicle-treated group) and conjunctiva (P=.048 vs control vehicle-treated group). Conclusion: Application of topical anti-VLA-4 sm led to a significant decrease in dry eye signs and suppression of inflammatory changes at the cellular and molecular levels.