Pathologic angiogenesis is a major feature of several blinding retinal diseases including age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity. Epigenetics has only recently been investigated for its role in intraocular angiogenesis.

Epigenetic regulation of angiogenesis can be mediated via DNA methylation, histone acetylation or microRNA. In this study, the role of the histone deacetylase inhibitor trichostatin A (TSA) was evaluated for its ability to inhibit angiogenesis in vitro and experimental choroidal neovascularization (CNV). TSA inhibited RPE cell proliferation, arrested the cell cycle at G1/S phase and suppressed cell migration. TSA treatment resulted in down-regulation of HIF-1a, and VEGF and up-regulation of PEDF in RPE. TSA decreased expression of VEGFR2 in choroidal endothelial cell (CEC). As well, TSA induced the activation of p38, and caspase 3 and inhibited activation of Akt in CEC. In mice, TSA attenuated laser-induced CNV, as seen by the reduced leakage in fluorescein angiography, smaller lesion sizes in histological analysis, and decreased CNV volumes. This study suggests that histone deacetylase inhibitors should be further evaluated for their therapeutic potential in ocular angiogenesis.