Potential Effect of Imeglimin on Mitochondrial Function in Subsynovial Connective Tissue of Idiopathic Carpal Tunnel...

Patients with idiopathic carpal tunnel syndrome (CTS) exhibit impaired mitochondrial function in the subsynovial connective tissue (SSCT) of the carpal tunnel. We hypothesized that Imeglimin, a compound known to enhance mitochondrial function, may improve mitochondrial activity in SSCT from these patients. This study aimed to evaluate the effects of Imeglimin on mitochondrial function in SSCT-derived cells obtained from patients with idiopathic CTS. SSCT samples were collected from 15 patients (mean age: 67.5  ±  9.7 years) who underwent carpal tunnel release surgery between April 2022 and March 2024. The cells were cultured under control conditions (Dulbecco's Modified Eagle Medium alone) or with 100 µM Imeglimin for 24 h. Mitochondrial function was assessed using multiple assays, including cell proliferation, superoxide dismutase (SOD) activity, apoptosis rate, mitochondrial volume, membrane potential, reactive oxygen species (ROS) production, gene expression related to mitochondrial biogenesis and antioxidant capacity, mitochondrial permeability transition pore opening, and ultrastructure by transmission electron microscopy. Statistical analyses were performed using the Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, and Fisher's protected least significant difference test, with p  <  0.05 considered significant. Compared with the control group, the Imeglimin-treated group showed significantly increased cell proliferation, SOD activity, mitochondrial membrane potential, mitochondrial volume, cristae density, and expression of genes related to mitochondrial biogenesis and antioxidant defense. Apoptosis and mitochondrial ROS production were significantly reduced (p <  0.05). These findings suggest that Imeglimin may enhance mitochondrial function in SSCT-derived cells from patients with idiopathic CTS, offering a potential therapeutic strategy for mitochondrial dysfunction in CTS.