Woo Jong Eun, Park Woo Chan, Yoo Young Hyun, Kim Sang Woo
Department of Ophthalmology, Ulsan University of College of Medicine , Ulsan , South Kore and.
Curr Eye Res. 2014 Apr;39(4):348-58. doi: 10.3109/02713683.2013.859272. Epub 2014 Jan 8.
This study was undertaken to evaluate the efficacy of co-treatment with suberoylanilide hydroxamic acid (SAHA) and mitomycin-C (MMC) on corneal fibrosis in an in-vivo model.
We examined the effect of co-treatment with MMC and SAHA, a potent histone deacetylase inhibitor (HDACi), on the corneal fibrosis and haze produced in rats following photorefractive keratectomy (PRK). We further examined the toxicity of this co-treatment on human corneal epithelial (HCE) cells in-vitro.
The combination of MMC and SAHA efficiently suppressed corneal fibrosis and haze following PRK. At the doses tested, SAHA had no inhibitory effect on human corneal epithelial cell viability, whereas MMC-treated cells showed increased apoptotic changes in Western blot testing and a fluorescence-activated cell sorting system. Co-treatment with SAHA and a low-dose of MMC minimized corneal haze after PRK and produced a significantly lower level of cytotoxic effects than treatment with MMC alone.
Treatment with SAHA in combination with a low dose of MMC could be a novel and effective therapeutic strategy to suppress the proliferation of corneal myofibroblasts, thereby inhibiting corneal fibrosis or haze with minimal ocular surface toxicity.
本研究旨在评估在体内模型中，辛二酰苯胺异羟肟酸（SAHA）与丝裂霉素-C（MMC）联合治疗对角膜纤维化的疗效。
我们研究了MMC与强效组蛋白去乙酰化酶抑制剂（HDACi）SAHA联合治疗对大鼠准分子激光原位角膜磨镶术（PRK）后角膜纤维化和角膜混浊的影响。我们还进一步研究了这种联合治疗对体外培养的人角膜上皮（HCE）细胞的毒性。
MMC与SAHA联合使用能有效抑制PRK后的角膜纤维化和角膜混浊。在所测试的剂量下，SAHA对人角膜上皮细胞活力无抑制作用，而经MMC处理的细胞在蛋白质印迹检测和荧光激活细胞分选系统中显示出凋亡变化增加。SAHA与低剂量MMC联合治疗可使PRK后的角膜混浊降至最低，且与单独使用MMC治疗相比，产生的细胞毒性作用水平显著更低。
SAHA与低剂量MMC联合治疗可能是一种新型有效的治疗策略，可抑制角膜肌成纤维细胞的增殖，从而以最小的眼表毒性抑制角膜纤维化或角膜混浊。
