McKay Tina B, Sarker-Nag Akhee, Lyon Desiree', Asara John M, Karamichos Dimitrios
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Cell Biochem Funct. 2015 Jul;33(5):341-50. doi: 10.1002/cbf.3122. Epub 2015 Jul 14.
Corneal scarring is the result of a disease, infection or injury. The resulting scars cause significant loss of vision or even blindness. To-date, the most successful treatment is corneal transplantation, but it does not come without side effects. One of the corneal dystrophies that are correlated with corneal scarring is keratoconus (KC). The onset of the disease is still unknown; however, altered cellular metabolism has been linked to promoting the fibrotic phenotype and therefore scarring. We have previously shown that human keratoconus cells (HKCs) have altered metabolic activity when compared to normal human corneal fibroblasts (HCFs). In our current study, we present evidence that quercetin, a natural flavonoid, is a strong candidate for regulating metabolic activity of both HCFs and HKCs in vitro and therefore a potential therapeutic to target the altered cellular metabolism characteristic of HKCs. Targeted mass spectrometry-based metabolomics was performed on HCFs and HKCs with and without quercetin treatment in order to identify variations in metabolite flux. Overall, our study reveals a novel therapeutic target OF Quercetin on corneal stromal cell metabolism in both healthy and diseased states. Clearly, further studies are necessary in order to dissect the mechanism of action of quercetin.
角膜瘢痕是疾病、感染或损伤的结果。由此产生的瘢痕会导致严重的视力丧失甚至失明。迄今为止,最成功的治疗方法是角膜移植,但它并非没有副作用。与角膜瘢痕相关的一种角膜营养不良是圆锥角膜(KC)。该病的发病原因尚不清楚;然而,细胞代谢改变与促进纤维化表型进而导致瘢痕形成有关。我们之前已经表明,与正常人角膜成纤维细胞(HCFs)相比,人圆锥角膜细胞(HKCs)的代谢活性发生了改变。在我们目前的研究中,我们提供证据表明,天然黄酮类化合物槲皮素是体外调节HCFs和HKCs代谢活性的有力候选物,因此是针对HKCs改变的细胞代谢特征的一种潜在治疗方法。对有或没有槲皮素处理的HCFs和HKCs进行基于靶向质谱的代谢组学分析,以确定代谢物通量的变化。总体而言,我们的研究揭示了槲皮素在健康和疾病状态下对角膜基质细胞代谢的一种新的治疗靶点。显然,为了剖析槲皮素的作用机制,还需要进一步的研究。