Absence of Therapeutic Benefit of the Anti-Inflammatory Protein TSG-6 for Corneal Alkali Injury in a Rat Model.

Purpose: To investigate the therapeutic efficacy of tumor necrosis factor (TNF)-α stimulated gene/protein 6 (TSG-6) in a rat model of corneal alkali injury. Methods: Corneal alkali injury was produced by placing an NaOH-soaked filter paper disk on the central cornea of the right eye of an anesthetized male Lewis (LEW/Crl) rat. Recombinant human TSG-6, or an equal volume of phosphate-buffered saline (PBS), was administered intravenously (IV), by anterior chamber (AC) injection, or as a topical drop. The affected eyes were photographed daily using a dissecting microscope and documented for clinical time course analysis of corneal opacification. Corneal tissue was excised at pre-determined therapeutic endpoints, with subsequent qRT-PCR or histological analyses. Results: The continuous monitoring of corneal alkali injury progression revealed TSG-6 treatments do not show sufficient effectiveness in vivo regardless of IV injection, AC injection, or topical application. Corneal opacification and neovascularization were not diminished, and gene expression was not impacted by these treatments. However, both IV and AC administration of TSG-6 significantly suppressed pro-inflammatory cytokines compared to PBS-treated eyes. Conclusion: We conclude that the therapeutic potential of TSG-6 is insufficient in a rat corneal alkali injury model.

Comprehensive Modeling of Corneal Alkali Injury in the Rat Eye.

PURPOSE: To characterize the molecular, clinical, and histopathological profiles in the rat cornea after alkali injury over a 21-day period. METHODS: Alkali injury was induced in one eye of male Lewis rats. Corneal opacity and corneal neovascularization were assessed daily. Real-time qRT-PCR analysis and immunohistochemical staining were conducted to examine inflammation, neovascularization, and fibrosis. RESULTS: We found that within 2 hours of chemical exposure, corneal opacification rapidly developed with an acute increase in various cytokine expressions, while several cytokines demonstrated a secondary peak by day 7. Early neutrophil infiltration peaked at day 1 post-injury while macrophage infiltration peaked at day 7. Throughout the time course of the study, corneal opacity persisted and neovascularization, lymphangiogenesis, and fibrosis progressed. CONCLUSIONS: This study highlights the molecular, clinical, and histopathological changes throughout the progression of alkali injury in the rat cornea. These profiles will assist in the development of new strategies and therapies for ocular alkali injury.