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Effects of topical Janus kinase inhibition on ocular surface inflammation and immunity

William Stevenson1, Zahra Sadrai, Jing Hua

  • 1*Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA; and †Pfizer, Inc, Medicine Development Group, San Diego, CA.

Cornea
|December 18, 2013
PubMed
Abstract

Insights

Topical tofacitinib, a Janus kinase inhibitor, effectively reduced ocular inflammation and immune cell infiltration in mouse models of corneal injury and dry eye disease. This study highlights its potential for treating ocular surface inflammatory conditions.

Area of Science:

  • Ophthalmology
  • Immunology
  • Pharmacology

Background:

  • Ocular surface inflammation and immune dysregulation contribute to conditions like dry eye disease.
  • Janus kinase (JAK) inhibitors have shown therapeutic potential in various inflammatory conditions.

Purpose of the Study:

  • To investigate the efficacy of topical ophthalmic tofacitinib in modulating ocular surface inflammation and immunity.
  • To assess the effects of tofacitinib on immune cell infiltration and cytokine expression in experimental models.

Main Methods:

  • Administered topical 0.003% tofacitinib or vehicle to mice subjected to corneal thermocautery or desiccating stress.
  • Analyzed corneal and conjunctival immune cell populations using flow cytometry and gene expression using qRT-PCR.
  • Evaluated clinical disease severity via corneal fluorescein staining.

Main Results:

  • Tofacitinib decreased corneal infiltration of inflammatory cells (CD45+, Gr-1+, CD11b+) and suppressed key inflammatory cytokine transcripts (IL-1β, IL-6) after thermocautery.
  • In dry eye models, tofacitinib reduced corneal staining, CD11b+ cell infiltration, and modulated cytokine profiles (increased IL-1RA, decreased TNF, IL-23).
  • Tofacitinib also decreased conjunctival IL-17A and increased FoxP3 expression, indicating immune modulation.

Conclusions:

  • Topical ophthalmic tofacitinib effectively suppressed ocular surface inflammation and aberrant immune responses in experimental models.
  • These findings suggest that topical JAK inhibition is a promising therapeutic strategy for ocular surface inflammatory diseases.

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