Abstract / Summary
Objectives: Ferroptosis in lens epithelial cells (LECs) is increasingly recognized as a key pathological process in cataract formation, driven by oxidative stress, lipid peroxidation, and aberrant RNA modification. This study investigated the role of METTL14 in UVB-induced ferroptosis in LECs and explored the protective mechanism of melatonin (MT).
Materials and methods: mRNA and protein levels of METTL14 and ferroptosis-related markers (GPX4, SLC7A11) were quantified. Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione levels were measured to assess ferroptotic activity. Mitochondrial structure and function were evaluated using transmission electron microscopy, mitochondrial membrane potential analysis, and ATP quantification. In vitro, METTL14 knockdown was achieved via siRNA in UVB-irradiated LECs. In vivo, a UVB-induced rat cataract model was used to assess lens opacity, histopathological changes, and ferroptosis-related protein expression.
Results: UVB irradiation significantly up-regulated METTL14 expression and promoted ferroptosis in LECs. MT treatment reduced METTL14 expression, suppressed ferroptosis in vitro and in vivo, alleviated lipid peroxidation, and restored mitochondrial morphology and function. In rats, MT markedly decreased lens opacity and attenuated UVB-induced pathological alterations.
Conclusion: MT inhibits METTL14-mediated ferroptosis in LECs, reduces lipid peroxidation, and restores mitochondrial function, thereby slowing cataract progression. These findings highlight METTL14 as a critical regulator of ferroptosis and support MT as a promising therapeutic strategy for cataract prevention and treatment.