Reduction of ETV1 is Identified as a Prominent Feature of Age-Related Cataract

To identify the inactive genes in cataract lenses and explore their function in lens epithelial cells (LECs). Lens epithelium samples obtained from both age-related cataract (ARC) patients and normal donors were subjected to two forms of histone H3 immunoprecipitation: H3K9ac and H3K27me3 chromatin immunoprecipitation (ChIP), followed by ChIP-seq. The intersection set of “active genes in normal controls” and “repressed genes in cataract lenses” was identified. To validate the role of a specific gene, <i>ETV1</i>, within this set, quantitative polymerase chain reaction (qPCR), western blot, and immunofluorescence were performed using clinical lens epithelium samples. Small interference RNA (siRNA) was utilized to reduce the mRNA level of <i>ETV1</i> in cultured LECs. Following this, transwell assay and western blot was performed to examine the migration ability of the cells. Furthermore, RNA-seq analysis was conducted on both cell samples with <i>ETV1</i> knockdown and control cells. Additionally, the expression level of <i>ETV1</i> in LECs was examined using qPCR under H₂O₂ treatment. Six genes were identified in the intersection set of “active genes in normal controls” and “repressed genes in ARC lenses”. Among these genes, <i>ETV1</i> showed the most significant fold-change decrease in the cataract samples compared to the control samples. After <i>ETV1</i> knockdown by siRNA in cultured LECs, reduced cell migration was observed, along with a decrease in the expression of β-Catenin and Vimentin, two specific genes associated with cell migration. In addition, under the oxidative stress induced by H₂O₂ treatment, the expression level of <i>ETV1</i> in LECs significantly decreased. Based on the findings of this study, it can be concluded that <i>ETV1</i> is significantly reduced in human ARC lenses. The repression of <i>ETV1</i> in ARC lenses appears to contribute to the disrupted differentiation of lens epithelium, which is likely caused by the inhibition of both cell differentiation and migration processes.