Soluble Epoxide Hydrolase Inhibitors Improve Cornea Alkali Wound Healing

Area of Science:

• Ophthalmology
• Pharmacology
• Biochemistry

Background:

• Corneal alkali injuries are severe, leading to vision loss with no specific treatments.
• Epoxy fatty acids (EpFAs) possess anti-inflammatory and anti-fibrotic properties.
• Soluble epoxide hydrolase (sEH) metabolizes EpFAs; its inhibitors (sEHis) may prevent fibrosis.

Purpose of the Study:

• To investigate the role of sEH inhibitors (sEHis) in treating alkali-induced corneal wounds (NaOH and ammonia).
• To establish novel in vitro and in vivo models for corneal ammonia wound healing.
• To evaluate the therapeutic potential of topical sEHi administration for corneal injuries.

Main Methods:

• Induction of corneal alkali injuries (NaOH and ammonia) in mouse models.
• Treatment with soluble epoxide hydrolase inhibitors (sEHis).
• Assessment of corneal opacity, vascularization, and expression of fibrosis markers (αSMA, collagen III, fibronectin, Collagen I).
• Analysis of inflammatory cell infiltration (CD45+, F4/80+).
• In vitro studies using human corneal fibroblasts stimulated with TGFβ1.

Main Results:

• sEHis significantly reduced or eliminated corneal haze in NaOH-injured corneas.
• Ammonia-injured corneas treated with sEHis showed no vascularization and resolved haze.
• Treatment with sEHis decreased αSMA, collagen III, and fibronectin expression in both injury models.
• sEH knockout corneas exhibited reduced inflammation and matrix remodeling compared to wild-type.
• sEHi treatment reduced TGFβ1-induced αSMA and sEH expression in human corneal fibroblasts.

Conclusions:

• Soluble epoxide hydrolase inhibitors (sEHis) play a critical role in mitigating corneal alkali injury responses.
• Topical sEHi administration is an effective treatment for NaOH and ammonia-induced corneal wounds.
• sEHis demonstrate significant anti-fibrotic and anti-inflammatory effects in the cornea, offering a novel therapeutic approach.