Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva 49100, Israel.
Int J Mol Sci. 2019 Feb 7;20(3):714. doi: 10.3390/ijms20030714.
Choroidal neovascularization (CNV) is a complication of age-related macular degeneration and a major contributing factor to vision loss. In this paper, we show that in a mouse model of laser-induced CNV, systemic administration of Butyroyloxymethyl-diethyl phosphate (AN7), a histone deacetylase inhibitor (HDACi), significantly reduced CNV area and vascular leakage, as measured by choroidal flatmounts and fluorescein angiography. CNV area reduction by systemic AN7 treatment was similar to that achieved by intravitreal bevacizumab treatment. The expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF-2), and the endothelial cells marker CD31, was lower in the AN7 treated group in comparison to the control group at the laser lesion site. In vitro, AN7 facilitated retinal pigmented epithelium (RPE) cells tight junctions' integrity during hypoxia, by protecting the hexagonal pattern of ZO-1 protein in the cell borders, hence reducing RPE permeability. In conclusion, systemic AN7 should be further investigated as a possible effective treatment for CNV.
脉络膜新生血管（CNV）是年龄相关性黄斑变性的一种并发症，也是导致视力丧失的主要因素。在本文中，我们展示了在激光诱导的 CNV 小鼠模型中，全身给予丁酰氧甲基-二乙基磷酸酯（AN7），一种组蛋白去乙酰化酶抑制剂（HDACi），通过脉络膜平铺和荧光素血管造影测量，可显著减少 CNV 面积和血管渗漏。全身 AN7 治疗的 CNV 面积减少与玻璃体内贝伐单抗治疗相当。与对照组相比，在激光损伤部位，用 AN7 处理的组中血管内皮生长因子（VEGF）、成纤维细胞生长因子（FGF-2）和内皮细胞标志物 CD31 的表达降低。体外，AN7 通过保护细胞边界中 ZO-1 蛋白的六边形模式，在缺氧期间促进视网膜色素上皮（RPE）细胞紧密连接的完整性，从而降低 RPE 的通透性。总之，全身 AN7 可进一步作为治疗 CNV 的有效方法进行研究。
