LncRNA H19 Promotes H2O2-Induced Human Trabecular Meshwork Cell Injury and Extracellular Matrix Production by Regulating the miR-20a-5p/Smad4 Axis

Primary open-angle glaucoma is characterized by trabecular meshwork cell injury and excessive extracellular matrix deposition. Given the established involvement of long non-coding RNAs in primary open-angle glaucoma pathogenesis, this study investigates the role and mechanism of long non-coding RNA H19 in mediating trabecular meshwork cell dysfunction and extracellular matrix production. Hydrogen peroxide-treated human trabecular meshwork cells were used to establish in vitro primary open-angle glaucoma models. Cell viability and apoptosis were assessed via cell counting kit-8 and flow cytometry. Gene/protein expression of H19, Smad4, and extracellular matrix components (fibronectin, collagen I, and laminin) was evaluated by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. Subcellular H19 localization was determined by nuclear–cytoplasmic fractionation. The H19–miR-20a-5p–Smad4 regulatory axis was validated through luciferase reporter assays and rescue experiments across three characterized human trabecular meshwork cell strains. Hydrogen peroxide exposure induced concentration-dependent human trabecular meshwork cell injury and significantly upregulated H19 and Smad4 expression (p p p p p p Long non-coding RNA H19 facilitates hydrogen peroxide-induced human trabecular meshwork cell injury and extracellular matrix deposition primarily by orchestrating the miR-20a-5p/Smad4 axis, with additional modulation of transforming growth factor-beta/Smad and nuclear factor erythroid 2-related factor 2 pathways.