VDR Is a Novel Regulator of Cellular Senescence in Lens Epithelial Cells

Age-related cataracts (ARC) are a leading cause of blindness worldwide, with lens epithelial cell (LEC) senescence playing a key role in their progression. While oxidative stress and DNA damage are known to induce LEC senescence, the mechanisms that actively suppress or delay this process remain poorly understood. The vitamin D receptor (VDR), a nuclear receptor and transcription factor, has been implicated in various physiological processes, including calcium homeostasis, immune modulation, and cell proliferation. Additionally, VDR activation has been reported to protect against cellular aging and oxidative stress. However, the role of VDR in LEC senescence and its potential function in preventing ARC has not been fully elucidated. In this study, we investigated the role of VDR in regulating LEC senescence using the human lens epithelial cell line SRA01/04. VDR knockdown induced senescence markers, including increased SA-β-GAL activity, p21 expression, and γ-H2AX accumulation and reduced Lamin B1 expression. Additionally, VDR knockdown led to a significant increase in intracellular reactive oxygen species (ROS) levels. Conversely, VDR overexpression suppressed H₂O₂-induced senescence and enhanced the expression of antioxidant enzymes such as SOD2 and GPX1. These findings indicate that VDR modulates LEC senescence by regulating oxidative stress and antioxidant enzyme expression, suggesting that VDR may be a potential therapeutic target for ARC prevention. Further studies, particularly in vivo models, are necessary to validate these findings and explore the translational potential of targeting VDR in cataract therapy.