title: Epigenetic Modification Prevents Excessive Wound Healing and Scar Formation After Glaucoma Filtration Surgery.
abstract: The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).
  
  
  
  A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 μM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, α-smooth muscle actin (αSMA), and F-actin staining. Furthermore, SAHA-mediated acetylation of histones in corneal fibroblasts and conjunctiva were determined by Western blot analysis.
  
  
  
  Suberoylanilide hydroxamic acid treatment after GFS showed no signs of edema, corneal opacity, endophthalmitis, or cataract formation. Morphometric analysis of SAHA-treated eyes showed higher bleb length (P < 0.001), bleb area (P < 0.05), lower IOP (P < 0.01), and decreased vascularity compared to control. Furthermore, SAHA treatment showed significantly reduced levels of αSMA (P < 0.001), F-actin (P < 0.01), and collagen deposition (P < 0.05) at the sclerotomy site. In addition, SAHA treatment increased the acetylation status of H3 and H4 histones in corneal fibroblasts and conjunctiva.
  
  
  
  This study demonstrates that HDAC inhibition is an attractive pharmacologic target to modulate GFS wound healing, and SAHA, an HDACi, can be a useful adjunct to improve the GFS outcome.
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 2One-Health One-Medicine Ophthalmology and Vision Research Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Ajay
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 2One-Health One-Medicine Ophthalmology and Vision Research Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Govindaraj
authors.initials: G
authors.lastname: Anumanthan
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 3Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Marcos
authors.initials: M
authors.lastname: Reyes
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 3Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Huiyi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 3Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Brubaker
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 2One-Health One-Medicine Ophthalmology and Vision Research Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Saad
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 2One-Health One-Medicine Ophthalmology and Vision Research Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Suneel
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 3Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, United States.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Rieger
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 2One-Health One-Medicine Ophthalmology and Vision Research Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States 3Mason Eye Institute.
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Mohan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002921:Cicatrix / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D003228:Conjunctiva / Q000473:pathology; D003315:Cornea / Q000473:pathology; D004195:Disease Models, Animal; D057890:Epigenomics; D005260:Female; D018463:Filtering Surgery; D005901:Glaucoma / Q000473:pathology / Q000601:surgery*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007429:Intraocular Pressure / Q000187:drug effects; D058628:Myofibroblasts / Q000187:drug effects; D011817:Rabbits; D000077337:Vorinostat; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D003094:Collagen