- Journal of Refractive Surgery
- April 2012 - Volume 28 · Issue 4: 285-290
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.
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.
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.
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.
From Harry S. Truman Memorial Veterans’ Hospital (Tandon, Tovey, Waggoner, Sharma, Mohan), Mason Eye Institute, School of Medicine, (Tandon, Tovey, Waggoner, Sharma, Cowden, Mohan), and College of Veterinary Medicine, University of Missouri (Mohan), Columbia, Missouri; and the Department of Ob/Gyn, University of Florida, Gainesville, Florida (Gibson, Liu, Schultz).
Supported in part by grants RO1EY17294 (R.R.M.), R01EY005587 (G.S.S.) from National Eye Institute, Bethesda, Maryland; 1I01BX00035701 (R.R.M.) from Veteran Health Affairs, Washington, DC; and an unrestricted grant from Research to Prevent Blindness, New York, New York.
The authors have no financial or proprietary interests in the materials presented herein.
Correspondence: Rajiv R. Mohan, PhD, Mason Eye Institute, School of Medicine University of Missouri, 1 Hospital Dr, Columbia, MO 65212. Tel: 573.884.1449; Fax: 573.884.4100; E-mail: email@example.com
Received: June 06, 2011
Accepted: January 03, 2011
Posted Online: March 01, 2012