Sjögren's syndrome is an
autoimmune disease associated with
inflammation of exocrine glands with clinical manifestations of
dry eye and dry mouth.
Dry eye in this disease involves
inflammation of the ocular surface tissues - cornea and conjunctiva. While systemic blockade of adhesion molecules has been used to treat
autoimmune diseases, the purpose of this study was to determine the therapeutic efficacy of topical application of an
integrin α4 adhesion molecule antagonist in a mouse model of
dry eye associated with Sjögren's syndrome. To assess this spontaneously developed ocular surface
inflammation related to Sjögren's syndrome in TSP-1null mice (12 wks) was evaluated. Mice were treated with topical formulations containing 0.1%
dexamethasone or 30 mg/ml
GW559090 or vehicle control. Corneal
fluorescein staining and conjunctival goblet cell density were assessed. Real-time PCR analysis was performed to assess expression of the inflammatory marker IL-1β in the cornea and Tbet and RORγt in the draining lymph nodes. Ocular surface
inflammation was detectable in TSP-1null mice (≥12 wk old), which resulted in increased corneal
fluorescein staining indicative of corneal barrier disruption and reduced conjunctival goblet cell density. These changes were accompanied by increased corneal expression of IL-1β as compared to WT controls and an altered balance of Th1 (Tbet) and Th17 (RORγt) markers in the draining lymph nodes. Topically applied
dexamethasone and
GW559090 significantly reduced corneal
fluorescein staining compared to vehicle treatment (p = 0.023 and p < 0.001, respectively). This improved corneal barrier integrity upon adhesion molecule blockade was consistent with significantly reduced corneal expression of pro-inflammatory IL-1β compared to vehicle treated groups (p < 0.05 for both treatments). Significant improvement in goblet cell density was also noted in mice treated with 0.1%
dexamethasone and
GW559090 (p < 0.05 for both). We conclude that similar to topical
dexamethasone, topically administered
GW559090 successfully improved corneal barrier integrity and
inflammation in an established ocular surface disease associated with Sjögren's syndrome.