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

Abstract

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 α 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-α 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. Clinical Relevance Topical blockade of VLA-4 may be a novel therapeutic approach to treat the clinical signs and inflammatory changes accompanying dry eye disease