Anti-inflammatory effect of topical administration of tofacitinib on corneal inflammation

Area of Science:

• Ophthalmology
• Immunology
• Pharmacology

Background:

• Corneal inflammation is a significant cause of vision impairment.
• Janus kinase (JAK) signaling pathways play a crucial role in inflammatory responses.
• Current treatments for corneal inflammation have limitations.

Purpose of the Study:

• To evaluate the anti-inflammatory effect of topical tofacitinib on corneal inflammation.
• To investigate the molecular mechanisms underlying tofacitinib's action in alkali-burned corneas.
• To assess the potential of JAK inhibitors as a therapeutic strategy for corneal inflammatory diseases.

Main Methods:

• Alkali burn model in BALB/c mice corneas.
• Topical administration of tofacitinib or vehicle (PBS).
• Analysis of corneal vascularization, inflammatory cell infiltration (Gr-1, F4/80), and molecular markers (IFN-γ, p-STAT1, CXCL9, CXCL5, CCL7, CCL2, MMP-9, STAT1) via immunohistochemistry, laser capture microdissection, and quantitative PCR array.
• In vitro study using human fibroblasts treated with IFN-γ and tofacitinib.

Main Results:

• Topical tofacitinib significantly reduced corneal vascularization compared to PBS.
• Tofacitinib diminished the immunoreactivity of Gr-1, F4/80, IFN-γ, and phosphorylated STAT1.
• Expression of pro-inflammatory genes (CXCL9, CXCL5, CCL7, CCL2, MMP-9) and STAT1 was downregulated by tofacitinib.
• In vitro, tofacitinib inhibited IFN-γ-induced STAT1 phosphorylation in human fibroblasts.

Conclusions:

• Topical administration of tofacitinib effectively reduces corneal inflammation and associated vascularization.
• Tofacitinib exerts its anti-inflammatory effects by down-regulating JAK- and IFN-γ-related signaling pathways and molecules.
• Topical JAK inhibitors represent a promising therapeutic approach for managing corneal inflammation.