Cytoprotective Potential of N-Acetylcysteine in an In Vitro Model of Retinal Oxidative Injury

Purpose: Sodium iodate (NaIO₃) is a well-established oxidizing agent that induces oxidative stress (OS) in ARPE-19 cells, while antioxidants such as N-acetylcysteine (NAC) have demonstrated cytoprotective effects in retinal degeneration models. This study establishes an in vitro NaIO₃-induced OS disease model to investigate pathways involved in RPE damage and restoration, providing a platform for preclinical screening of antioxidant molecules. Methods: The cytoprotective effect of NAC on NaIO₃-induced OS in RPE cells was evaluated using CMFDA cell viability assay (2′,7′-dichlorofluorescin diacetate), JC-1 staining, colony-forming unit assay, scratch assay, PI/Annexin V staining, and gene expression analysis related to OS, inflammation, the cell cycle, and autophagy. Results: NAC treatment significantly decreased ROS levels and stabilized mitochondrial potential, increased cell viability and colony-forming ability, cell adhesion and migration potential. Furthermore, NAC prevented NaIO₃-induced cell death and modulated the expression of genes associated with OS, inflammation, cell cycle, and autophagy. Conclusion: The results showed successful establishment of a reproducible OS-based retinal degeneration model in ARPE-19 cells. Additionally, NAC exhibited significant cytoprotective activity against OS in RPE cells, highlighting its therapeutic potential as an antioxidant agent against retinal degeneration by reducing ROS levels, restoring mitochondrial membrane potential, and attenuating cell cycle dysregulation and inflammation.