A novel protein encoded by hsa_circ_0068626 contributes to age-related cataract via the p62/Keap1/Nrf2 signaling pathway-mediated ferroptosis.

This study investigates whether circular RNAs (circRNAs) modulate ferroptosis in lens epithelial cells (LECs) during age-related cataract (ARC) pathogenesis via novel encoded proteins. Initial circRNA-sequencing identified hsa_circ_0068626 (circTFRC) as significantly upregulated in ARC, predominantly localized to the cytoplasm through nuclear-cytoplasmic fractionation and fluorescence in situ hybridization (FISH). Functional assays revealed that circTFRC depletion impaired LECs proliferation and viability, while overexpression exacerbated ferroptosis, evidenced by elevated intracellular reactive oxygen species (ROS) and Fe level via fluorescence probes and flow cytometry.