Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Melatonin alleviates ferroptosis in lens epithelial cells via regulating METTL14 expression

Articles in Press

Document Type : Original Article

Authors
Huirui Liu 1, 2
Fengchun Kang 1, 2
Junyao Lu 2
Jialin Luo 1, 2
Yi Gao 1, 2
Zijian Yu 1
Qi An 1
Chen Yang 1
Liyao Sun 1
Hongyan Ge 1
1 Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China
2 The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital, Harbin Medical University, Harbin, China
10.22038/ijbms.2026.92837.20039
Abstract
Objective(s): 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.
Keywords
Cataract
Epithelial cells
Ferroptosis
Lens crystalline
Melatonin
N6-methyladenosine
Oxidative stress
Ultraviolet rays
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 11 August 2026