Vorinostat: A Potent Agent to Prevent and Treat Laser-induced Corneal Haze
| Autor: | Yuanjing Liu, Rajiv R. Mohan, Ashish Tandon, Daniel J. Gibson, John W. Cowden, Gregory S. Schultz, Ajay Sharma, Jonathan C.K. Tovey, Michael Waggoner |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty genetic structures medicine.medical_treatment Corneal Keratocytes Hydroxamic Acids Real-Time Polymerase Chain Reaction Photorefractive Keratectomy Article Cornea Transforming Growth Factor beta1 Corneal Opacity Postoperative Complications Fibrosis In vivo In Situ Nick-End Labeling Animals Humans Medicine RNA Messenger Vorinostat Cells Cultured Corneal Haze Dose-Response Relationship Drug business.industry LASIK medicine.disease Actins eye diseases Photorefractive keratectomy Fibronectins Histone Deacetylase Inhibitors Ophthalmology medicine.anatomical_structure Cancer research Female Surgery Rabbits sense organs Histone deacetylase business medicine.drug |
| Zdroj: | Journal of Refractive Surgery. 28:285-290 |
| ISSN: | 1081-597X |
| DOI: | 10.3928/1081597x-20120210-01 |
| Popis: | Approximately 80% of Americans older than 12 years have refractive errors.1 Laser eye surgeries such as photorefractive keratectomy (PRK), LASIK, and laser epithelial keratomileusis are frequently used to correct refractive errors and reduce dependency on spectacles or contact lenses.1–3 Photorefractive keratectomy is considered safest among refractive surgeries but is often associated with postoperative corneal haze in some cases.2,3 Extensive research revealed that excessive cytokine and growth factor activity in the stroma following PRK induces abnormal corneal wound healing, extracellular matrix deposition, keratocyte transformation to myofibroblasts, and haze formation in the cornea.4–10 Among many cytokines, transforming growth factor beta 1 (TGFβ1) has been identified to play a major role in haze development, triggering transformation of quiescent keratocytes into corneal fibroblasts and myofibroblasts.6–10 Selective modulation of TGFβ1 has emerged as an effective strategy to control laser-induced corneal haze.7–10 Histone acetyltransferase and histone deacetylase (HDAC) are enzymes involved in epigenetic regulation of DNA transcriptional activity via acetylation-deacetylation of histone proteins including TGFβ1.11–14 Histone deacetylase inhibitors are shown to reduce TGFβ1-induced collagen synthesis, myofibroblast formation, and fibrosis in many tissues including the cornea.12–14 In line with our hypothesis that epigenetic modulation is a novel and effective approach to treat corneal haze, we found significant inhibition of TGFβ1-mediated human corneal fibroblast transformation to myofibroblasts in vitro and PRK-induced corneal haze in rabbits in vivo by a potent HDAC inhibitor, trichostatin-A.14 Unfortunately, it is not approved for human use; however, in 2006 an analog of trichostatin-A, vorinostat (suberoylanilide hydroxamic acid) was approved by the United States Food and Drug Administration for medical use. Currently, vorinostat is used clinically to treat cancer in human patients. The purpose of this study was to evaluate the usefulness of vorinostat in preventing postoperative PRK corneal haze by testing its efficacy and toxicity using in vivo PRK corneal haze rabbit and in vitro TGFβ1-induced corneal fibrosis models. |
| Databáze: | OpenAIRE |
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