title: Vorinostat: a potent agent to prevent and treat laser-induced corneal haze.
abstract: OBJECTIVE
  This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro.
  
  
  METHODS
  Corneal haze in rabbits was produced with -9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 hours for in vitro studies. Slit-lamp microscopy, TUNEL assay, and trypan blue were used to determined vorinostat toxicity, whereas real-time polymerase chain reaction, immunocytochemistry, and immunoblotting were used to measure its efficacy.
  
  
  RESULTS
  Single 5-minute vorinostat (25 μm) topical application on the cornea following PRK significantly reduced corneal haze (P<.008) and fibrotic marker proteins (α-smooth muscle actin and f-actin; P<.001) without showing redness, swelling, or inflammation in rabbit eyes in vivo screened 4 weeks after PRK. Vorinostat reduced TGFβ1-induced fibrosis in human and rabbit corneas in vitro in a dose-dependent manner without altering cellular viability, phenotype, or proliferation.
  
  
  CONCLUSIONS
  Vorinostat is non-cytotoxic and safe for the eye and has potential to prevent laser-induced corneal haze in patients undergoing PRK for high myopia.
authors.affiliation: Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri 65212, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Tandon
authors.forename: Jonathan C K
authors.initials: JC
authors.lastname: Tovey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Waggoner
authors.forename: Ajay
authors.initials: A
authors.lastname: Sharma
authors.forename: John W
authors.initials: JW
authors.lastname: Cowden
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gibson
authors.forename: Yuanjing
authors.initials: Y
authors.lastname: Liu
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Schultz
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Mohan
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects / Q000601:surgery*; D060527:Corneal Keratocytes / Q000187:drug effects; D003318:Corneal Opacity / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis / Q000139:chemically induced / Q000517:prevention & control; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D018903:Photorefractive Keratectomy; D011183:Postoperative Complications / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D000077337:Vorinostat
chemical_list: D000199:Actins; D005353:Fibronectins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000077337:Vorinostat