Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, University of Fukui, Fukui, Japan.
Technical Division, School of Engineering, University of Fukui, Fukui, Japan.
Genes Cells. 2024 Oct;29(10):876-888. doi: 10.1111/gtc.13150. Epub 2024 Sep 1.
Cataracts are a disease that reduces vision due to opacity formation of the lens. Diabetic cataracts occur at young age and progress relatively quickly, so the development of effective treatment has been awaited. Several studies have shown that pyruvate inhibits oxidative stress and glycation of lens proteins, which contribute to onset of diabetic cataracts. However, detailed molecular mechanisms have not been revealed. In this study, we attempted to reduce galactose-induced opacity by pyruvate with rat ex vivo model. Rat lenses were extracted and cultured in galactose-containing medium to induce lens opacity. After opacity had developed, continued culturing with pyruvate in the medium resulted in a reduction of lens opacity. Subsequently, we conducted microarray analysis to investigate the genes that contribute to the therapeutic effect. We performed quantitative expression measurements using RT-qPCR for extracted genes that were upregulated in cataract-induced lenses and downregulated in pyruvate-treated lenses, resulting in the identification of 34 candidate genes. Functional analysis using the STRING database suggests that metallothionein-related factors (Mt1a, Mt1m, and Mt2A) and epithelial-mesenchymal transition-related factors (Acta2, Anxa1, Cd81, Mki67, Timp1, and Tyms) contribute to the therapeutic effect of cataracts.
白内障是一种由于晶状体混浊导致视力下降的疾病。糖尿病性白内障在年轻时发生，且进展相对较快，因此一直期待着有效的治疗方法的发展。多项研究表明，丙酮酸可抑制导致糖尿病性白内障发生的晶状体蛋白氧化应激和糖基化。然而，其详细的分子机制尚未被揭示。在本研究中，我们尝试使用丙酮酸来减轻体外培养的大鼠晶状体中由半乳糖诱导的混浊。将大鼠晶状体提取并在含有半乳糖的培养基中培养，以诱导晶状体混浊。在混浊形成后，继续在培养基中用丙酮酸培养可降低晶状体混浊。随后，我们进行了微阵列分析，以研究对治疗效果有贡献的基因。我们使用 RT-qPCR 对提取的基因进行了定量表达测量，这些基因在白内障诱导的晶状体中上调，在丙酮酸处理的晶状体中下调，鉴定出 34 个候选基因。使用 STRING 数据库进行的功能分析表明，金属硫蛋白相关因子（Mt1a、Mt1m 和 Mt2A）和上皮-间充质转化相关因子（Acta2、Anxa1、Cd81、Mki67、Timp1 和 Tyms）有助于白内障的治疗效果。
