Takashima Masaru, Yamamura Shunki, Tamiya Chie, Inami Mayumi, Takamura Yoshihiro, Inatani Masaru, Oki Masaya
Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan.
Technical Division, School of Engineering, University of Fukui, Fukui, Japan.
Sci Rep. 2024 Feb 19;14(1):4123. doi: 10.1038/s41598-024-54559-y.
Although cataract is the leading cause of blindness worldwide, the detailed pathogenesis of cataract remains unclear, and clinically useful drug treatments are still lacking. In this study, we examined the effects of glutamate using an ex vivo model in which rat lens is cultured in a galactose-containing medium to induce opacity formation. After inducing lens opacity formation in galactose medium, glutamate was added, and the opacity decreased when the culture was continued. Next, microarray analysis was performed using samples in which the opacity was reduced by glutamate, and genes whose expression increased with galactose culture and decreased with the addition of glutamate were extracted. Subsequently, STRING analysis was performed on a group of genes that showed variation as a result of quantitative measurement of gene expression by RT-qPCR. The results suggest that apoptosis, oxidative stress, endoplasmic reticulum (ER) stress, cell proliferation, epithelial-mesenchymal transition (EMT), cytoskeleton, and histones are involved in the formation and reduction of opacity. Therefore, glutamate may reduce opacity by inhibiting oxidative stress and its downstream functions, and by regulating the cytoskeleton and cell proliferation.
尽管白内障是全球失明的主要原因，但白内障的详细发病机制仍不清楚，临床上也缺乏有效的药物治疗方法。在本研究中，我们使用体外模型研究了谷氨酸的作用，该模型是将大鼠晶状体培养在含半乳糖的培养基中以诱导晶状体混浊形成。在半乳糖培养基中诱导晶状体混浊形成后，加入谷氨酸，继续培养时混浊度降低。接下来，对谷氨酸降低混浊度的样本进行微阵列分析，提取出在半乳糖培养时表达增加而添加谷氨酸后表达降低的基因。随后，对通过RT-qPCR定量测量基因表达而显示出变化的一组基因进行STRING分析。结果表明，细胞凋亡、氧化应激、内质网（ER）应激、细胞增殖、上皮-间质转化（EMT）、细胞骨架和组蛋白参与了混浊的形成和减轻。因此，谷氨酸可能通过抑制氧化应激及其下游功能，以及调节细胞骨架和细胞增殖来降低混浊度。
