The efficacy of co-treatment with suberoylanilide hydroxamic acid and mitomycin C on corneal scarring after therapeutic keratectomy: an animal study.

Abstract

PURPOSE:

This study was undertaken to evaluate the efficacy of co-treatment with suberoylanilide hydroxamic acid (SAHA) and mitomycin-C (MMC) on corneal fibrosis in an in-vivo model.

MATERIALS AND METHODS:

We examined the effect of co-treatment with MMC and SAHA, a potent histone deacetylase inhibitor (HDACi), on the corneal fibrosis and haze produced in rats following photorefractive keratectomy (PRK). We further examined the toxicity of this co-treatment on human corneal epithelial (HCE) cells in-vitro.

RESULTS:

The combination of MMC and SAHA efficiently suppressed corneal fibrosis and haze following PRK. At the doses tested, SAHA had no inhibitory effect on human corneal epithelial cell viability, whereas MMC-treated cells showed increased apoptotic changes in Western blot testing and a fluorescence-activated cell sorting system. Co-treatment with SAHA and a low-dose of MMC minimized corneal haze after PRK and produced a significantly lower level of cytotoxic effects than treatment with MMC alone.

CONCLUSIONS:

Treatment with SAHA in combination with a low dose of MMC could be a novel and effective therapeutic strategy to suppress the proliferation of corneal myofibroblasts, thereby inhibiting corneal fibrosis or haze with minimal ocular surface toxicity.

• Authors: Jong Eun Woo, Woo Chan Park, Young Hyun Yoo, Sang Woo Kim
• Journal: Current eye research (Curr Eye Res) Vol. 39 Issue 4 Pg. 348-58 (Apr 2014) ISSN: 1460-2202 [Electronic] England
• PMID: 24401036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Nucleic Acid Synthesis Inhibitors
• Mitomycin
• Vorinostat

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line
• Cell Survival
• Cicatrix (drug therapy, etiology, pathology)
• Corneal Diseases (drug therapy, etiology, pathology)
• Cytokines (metabolism)
• Disease Models, Animal
• Drug Therapy, Combination
• Epithelium, Corneal (drug effects, metabolism, pathology)
• Fibrosis (drug therapy, etiology, pathology)
• Histone Deacetylase Inhibitors (therapeutic use)
• Humans
• Hydroxamic Acids (therapeutic use)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Mitomycin (therapeutic use)
• Nucleic Acid Synthesis Inhibitors (therapeutic use)
• Photorefractive Keratectomy (adverse effects)
• Rats
• Rats, Sprague-Dawley
• Treatment Outcome
• Vorinostat