Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan.
Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
PLoS One. 2024 Feb 28;19(2):e0299145. doi: 10.1371/journal.pone.0299145. eCollection 2024.
Cataract is an eye disease, in which the lens becomes opaque, causing vision loss and blindness. The detailed mechanism of cataract development has not been characterized, and effective drug therapies remain unavailable. Here, we investigated the effects of Hypoxia-inducible factor 1 (HIF-1) inhibitors using an ex vivo model, in which rat lenses were cultured in galactose-containing medium to induce opacity formation. We found that treatment with the HIF-1 inhibitors 2-Methoxyestradiol (2ME2), YC-1, and Bavachinin decreased lens opacity. Microarray analysis on 2ME2-treated samples, in which opacity was decreased, identified genes upregulated by galactose and downregulated by inhibitor treatment. Subsequent STRING analysis on genes that showed expression change by RT-qPCR identified two clusters. First cluster related to the cytoskeleton and epithelial-mesenchymal transition (EMT). Second cluster related to the oxidative stress, and apoptosis. ACTA2, a known marker for EMT, and TXNIP, a suppressor of cell proliferation and activator of apoptosis, were present in each cluster. Thus, suppression of EMT and apoptosis, as well as activation of cell proliferation, appear to underlie the decrease in lens opacity.
白内障是一种眼部疾病，其中晶状体变得不透明，导致视力丧失和失明。白内障发展的详细机制尚未确定，有效的药物治疗仍然缺乏。在这里，我们使用体外模型研究了缺氧诱导因子 1（HIF-1）抑制剂的作用，在该模型中，将大鼠晶状体在含有半乳糖的培养基中培养以诱导不透明度形成。我们发现，用 HIF-1 抑制剂 2-甲氧基雌二醇（2ME2）、YC-1 和巴维辛处理可降低晶状体混浊度。用 2ME2 处理的样品进行微阵列分析，其中混浊度降低，鉴定出由半乳糖上调和抑制剂处理下调的基因。随后对 RT-qPCR 显示表达变化的基因进行 STRING 分析，确定了两个簇。第一个簇与细胞骨架和上皮-间充质转化（EMT）有关。第二个簇与氧化应激和细胞凋亡有关。EMT 的已知标志物 ACTA2 和细胞增殖抑制剂和细胞凋亡激活剂 TXNIP 存在于每个簇中。因此，抑制 EMT 和细胞凋亡以及激活细胞增殖似乎是降低晶状体混浊度的基础。
