Abstract
Purpose :
Histone deacetylases (HDACs) plays a causative role in cancer and central nervous diseases by modification of histone and non-histone protein. Downregulation of HDAC expression by HDAC inhibitors (HDACis) restores or increases the level of histone acetylation and shows the potential approach to treat tumorigenesis and angiogenesis. In this study, we examined the effect of panobinostat, a non-selective HDACis, on inflammatory corneal angiogenesis.
Methods :
Corneal inflammation was induced with 1 N NaOH. Panobinostat was applied topically to the injury corneas twice a day for 7 days. Eyes were examined with a slit lamp (Zeiss, Germany) 7 and 14 days after alkali injury. Mice were sacrificed and the corneas were removed from both eyes for total RNA extraction or histological analysis. In vitro, the effect of panobinostat on migration, proliferation and tube formation by human microvascular endothelial cells (HEMC-1) was examined. Total RNA of corneas and HEMC-1 were performed by real time PCR to examine the expression of pro/ anti-angiogenic factors. Experiments were repeated at least 3 times.
Results :
Topical application of panobinostat to the injured corneas attenuated corneal neovascularization (CNV) in an alkali-induced corneal injury model. In addition, in vivo treatment with panobinostat downregulated the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGF-β1), and epidermal growth factor (EGF), but upregulated the expression of the anti-angiogenic factors thrombospondin (TSP)-1, TSP-2, and ADAMTS-1 in the injured corneas. Furthermore, panobinostat inhibited the expression of pro-angiogenic factors, migration, proliferation, and tube formation by human microvascular endothelial cells (HEMC-1) in vitro.
Conclusions :
We found that topical application of panobinostat attenuated CNV by inhibition of the expression of the pro-angiogenic factors. The data suggest that panobinostat has therapeutic potential for angiogenesis-associated diseases such as CNV.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.