Astaxanthin Alleviates H2O2-Induced Oxidative Damage in ARPE-19 Cells: APLN, GNA12, and SNAI1 as Candidate Mediators

Objective: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among middle-aged and elderly populations globally. Oxidative stress-mediated retinal pigment epithelium (RPE) cell injury represents the core initiating pathological mechanism. Astaxanthin, a potent natural antioxidant, can efficiently penetrate the blood–retinal barrier and specifically accumulate in ocular tissues, demonstrating substantial potential in AMD prevention and treatment. However, its specific antioxidative molecular mechanisms remain incompletely elucidated. This study aims to investigate whether APLN, GNA12, and SNAI1 serve as potential regulatory targets through which astaxanthin alleviates oxidative stress injury in RPE cells. Methods: We established a H2O2-induced oxidative stress model in ARPE-19 cells, assessed cell viability and SOD activity, screened hub genes via transcriptome sequencing and WGCNA, validated gene expression by qRT-PCR, and characterized target binding interactions via molecular docking and dynamics simulations. Results: Exposure to 1000 μM H2O2, employed to induce oxidative stress injury, decreased cell viability to 55.5%. Treatment with 20 μM astaxanthin significantly reduced cell damage caused by H2O2, improved cell viability to 82.69%, and greatly increased SOD activity. Bioinformatics identified 22 core hub genes, with APLN, GNA12, and SNAI1 as key dysregulated genes. qRT-PCR confirmed astaxanthin significantly upregulated APLN and GNA12 and downregulated SNAI1, while molecular docking and dynamics simulations suggested potential binding to APLNR, GNA12, and SNAI1. Conclusions: Astaxanthin can alleviate oxidative-stress-induced damage in RPE cells and exert antioxidant properties, potentially through candidate target genes APLN, GNA12, and SNAI1.