Kagan Dov B, Liu Hong, Hutnik Cindy Ml
Ivey Eye Institute, St Joseph's Hospital, London, ON, Canada.
Clin Ophthalmol. 2012;6:1471-6. doi: 10.2147/OPTH.S35139. Epub 2012 Sep 7.
Oxidative stress induced retinal pigment epithelium (RPE) dysfunction is hypothesized to be fundamental in the pathogenesis of age-related macular degeneration (AMD). This study investigated whether vitamin C, vitamin C phosphate, vitamin E, propofol, betaxolol, and N-acetyl cysteine (NAC) protect human RPE cells from oxidative stress.
ARPE-19 cells were pretreated with the compounds under investigation. The chemical oxidant tert-butyl hydroperoxide (t-BOOH) was used to induce oxidative stress. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
Exposure to t-BOOH resulted in a dose- and time-dependent reduction in ARPE-19 cell viability. Compared with cells given t-BOOH alone, vitamin E and NAC pretreated cells had significantly improved viability, propofol and betaxolol pretreated cells had no significant difference in viability, and vitamin C and vitamin C phosphate pretreated cells had significantly reduced viability.
Of the compounds studied, only vitamin E and NAC significantly mitigated the effects of oxidative stress on RPE cells. Because of their potential therapeutic value for AMD patients, these and other RPE protective compounds continue to merit further investigation.
氧化应激诱导的视网膜色素上皮(RPE)功能障碍被认为是年龄相关性黄斑变性(AMD)发病机制的基础。本研究调查了维生素C、维生素C磷酸盐、维生素E、丙泊酚、倍他洛尔和N-乙酰半胱氨酸(NAC)是否能保护人RPE细胞免受氧化应激的影响。
用所研究的化合物预处理ARPE-19细胞。使用化学氧化剂叔丁基过氧化氢(t-BOOH)诱导氧化应激。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法测定细胞活力。
暴露于t-BOOH导致ARPE-19细胞活力呈剂量和时间依赖性降低。与单独给予t-BOOH的细胞相比,维生素E和NAC预处理的细胞活力显著提高,丙泊酚和倍他洛尔预处理的细胞活力无显著差异,维生素C和维生素C磷酸盐预处理的细胞活力显著降低。
在所研究的化合物中,只有维生素E和NAC能显著减轻氧化应激对RPE细胞的影响。由于它们对AMD患者具有潜在的治疗价值,这些以及其他RPE保护化合物仍值得进一步研究。