PMID- 22386369
OWN - NLM
STAT- MEDLINE
DCOM- 20120522
LR  - 20220410
IS  - 1081-597X (Print)
IS  - 1081-597X (Linking)
VI  - 28
IP  - 4
DP  - 2012 Apr
TI  - Vorinostat: a potent agent to prevent and treat laser-induced corneal haze.
PG  - 285-90
LID - 10.3928/1081597X-20120210-01 [doi]
AB  - PURPOSE: 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 (TGFbeta1) -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 TGFbeta1. Vorinostat (25 mum) 
      was topically applied once for 5 minutes on rabbit cornea immediately after PRK 
      for in vivo studies. Vorinostat (0 to 25 mum) 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 mum) topical 
      application on the cornea following PRK significantly reduced corneal haze 
      (P<.008) and fibrotic marker proteins (alpha-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 TGFbeta1-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.
CI  - Copyright 2012, SLACK Incorporated.
FAU - Tandon, Ashish
AU  - Tandon A
AD  - Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri 65212, USA.
FAU - Tovey, Jonathan C K
AU  - Tovey JC
FAU - Waggoner, Michael R
AU  - Waggoner MR
FAU - Sharma, Ajay
AU  - Sharma A
FAU - Cowden, John W
AU  - Cowden JW
FAU - Gibson, Daniel J
AU  - Gibson DJ
FAU - Liu, Yuanjing
AU  - Liu Y
FAU - Schultz, Gregory S
AU  - Schultz GS
FAU - Mohan, Rajiv R
AU  - Mohan RR
LA  - eng
GR  - R01EY17294/EY/NEI NIH HHS/United States
GR  - R01 EY017294/EY/NEI NIH HHS/United States
GR  - R01 EY005587/EY/NEI NIH HHS/United States
GR  - R01EY005587/EY/NEI NIH HHS/United States
GR  - P30 EY021721/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120301
PL  - United States
TA  - J Refract Surg
JT  - Journal of refractive surgery (Thorofare, N.J. : 1995)
JID - 9505927
RN  - 0 (Actins)
RN  - 0 (Fibronectins)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 58IFB293JI (Vorinostat)
SB  - IM
MH  - Actins/genetics
MH  - Animals
MH  - Cells, Cultured
MH  - Cornea/drug effects/*surgery
MH  - Corneal Keratocytes/drug effects
MH  - Corneal Opacity/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fibronectins/genetics
MH  - Fibrosis/chemically induced/prevention & control
MH  - Histone Deacetylase Inhibitors/adverse effects/*therapeutic use
MH  - Humans
MH  - Hydroxamic Acids/adverse effects/*therapeutic use
MH  - In Situ Nick-End Labeling
MH  - *Photorefractive Keratectomy
MH  - Postoperative Complications/*prevention & control
MH  - RNA, Messenger/metabolism
MH  - Rabbits
MH  - Real-Time Polymerase Chain Reaction
MH  - Transforming Growth Factor beta1/pharmacology
MH  - Vorinostat
PMC - PMC4508025
MID - NIHMS527346
COIS- The authors have no financial or proprietary interests in the materials presented 
      herein.
EDAT- 2012/03/06 06:00
MHDA- 2012/05/23 06:00
PMCR- 2015/07/20
CRDT- 2012/03/06 06:00
PHST- 2011/06/06 00:00 [received]
PHST- 2011/01/03 00:00 [accepted]
PHST- 2012/03/06 06:00 [entrez]
PHST- 2012/03/06 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
PHST- 2015/07/20 00:00 [pmc-release]
AID - 10.3928/1081597X-20120210-01 [doi]
PST - ppublish
SO  - J Refract Surg. 2012 Apr;28(4):285-90. doi: 10.3928/1081597X-20120210-01. Epub 
      2012 Mar 1.