Long noncoding RNA glutathione peroxidase 3-antisense inhibits lens epithelial cell apoptosis by upregulating glutathione peroxidase 3 expression in age-related cataract.

Purpose:Age-related cataract (ARC) is the leading cause of visual impairment and blindness worldwide. The apoptosis of lens epithelial cells (LECs) induced by oxidative damage is a major contributing factor to ARC. Long noncoding RNAs (lncRNAs) play important roles in various biologic processes. We aimed to explore the role of glutathione peroxidase 3 (GPX3)-antisense (AS) in ARCs. Methods:We extracted total RNAs from transparent and age-matched cataractous human lenses and detected lncRNA expression profiles using high-throughput RNA sequencing. The expression of GPX3-AS and GPX3 was detected by quantitative real-time PCR (qRT-PCR). Apoptotic proteins were detected by western blot and immunofluorescence. We treated SRA01/04 cells with H₂O₂ to mimic oxidative stress and induce cell apoptosis, which was analyzed by flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. The cell counting kit-8 (CCK-8) assay was used to detect the viability of SRA01/04 cells. The location of GPX3-AS was determined by fluorescence in situ hybridization (FISH) and cell nuclear and cytoplasmic RNA separation. Results:The lncRNA GPX3-AS, which is located in the nuclei of LECs, was downregulated in cataractous human lenses compared with control lenses, and proapoptotic proteins were expressed at high levels in the anterior lens capsules of ARC tissues. An in vitro study suggested that GPX3-AS inhibited H₂O₂-induced SRA01/04 cell apoptosis. As GPX3-AS is transcribed from the AS strand of the GPX3 gene locus, we further revealed its regulatory role in GPX3 expression. GPX3-AS was positively correlated with GPX3 expression. In addition, GPX3-AS inhibited H₂O₂-induced SRA01/04 cell apoptosis by upregulating GPX3 expression. Conclusions:In summary, our study revealed that GPX3-AS downregulated the apoptosis of LECs via promoting GPX3 expression, implying a novel therapeutic target for ARCs.

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