Modulation of integrin α4 β1 (VLA-4) in dry eye disease

Tatiana Ecoiffier, Jaafar El-Annan, Saadia Rashid, Debra Schaumberg, Reza Dana

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1695-1699
Number of pages5
JournalArchives of Ophthalmology
Volume126
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

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Integrin alpha4beta1
Eye Diseases
Integrins
Conjunctiva
Fluorescein
Staining and Labeling
T-Lymphocytes
Cornea
Tumor Necrosis Factor-alpha
Dry Eye Syndromes
Controlled Environment
Real-Time Polymerase Chain Reaction
Cell Count
Cytokines
Messenger RNA

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Modulation of integrin α4 β1 (VLA-4) in dry eye disease. / Ecoiffier, Tatiana; El-Annan, Jaafar; Rashid, Saadia; Schaumberg, Debra; Dana, Reza.

In: Archives of Ophthalmology, Vol. 126, No. 12, 12.2008, p. 1695-1699.

Research output: Contribution to journalArticle

Ecoiffier, T, El-Annan, J, Rashid, S, Schaumberg, D & Dana, R 2008, 'Modulation of integrin α4 β1 (VLA-4) in dry eye disease', Archives of Ophthalmology, vol. 126, no. 12, pp. 1695-1699. https://doi.org/10.1001/archopht.126.12.1695
Ecoiffier, Tatiana ; El-Annan, Jaafar ; Rashid, Saadia ; Schaumberg, Debra ; Dana, Reza. / Modulation of integrin α4 β1 (VLA-4) in dry eye disease. In: Archives of Ophthalmology. 2008 ; Vol. 126, No. 12. pp. 1695-1699.
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