Baicalin Protects ARPE-19 Cells Against BRVO-Related Hypoxic Injury by Preserving Mitochondrial Function and Inhibiting Ferroptosis

Branch retinal vein occlusion (BRVO) is a retinal vascular disorder characterized by ischemia and hypoxia. These pathological conditions contribute to retinal pigment epithelial (RPE) cell injury through oxidative stress and ferroptosis. However, whether baicalin (BC) protects against hypoxia-induced RPE injury remains unclear. CoCl2-induced hypoxic ARPE-19 cells were used to evaluate the protective effects and potential mechanisms of BC. BC improved cell viability and reduced LDH release under hypoxic conditions. BC markedly suppressed hypoxia-induced inflammatory responses, as evidenced by reduced p65 and ICAM-1 expression and decreased release of pro-inflammatory cytokines. Moreover, BC alleviated oxidative stress by reducing ROS and MDA accumulation and restoring SOD and GSH activity. BC attenuated mitochondrial dysfunction, accompanied by restoration of mitochondrial membrane potential, oxygen consumption rate (OCR), and ATP production. Transmission electron microscopy (TEM) results further confirmed the protective effect of BC on mitochondrial integrity. Mechanistically, BC suppressed ferroptosis by reducing intracellular Fe2+ accumulation and lipid peroxidation, accompanied by downregulation of TFR1, ACSL4, and p53, as well as upregulation of SLC7A11 and GPX4. These findings suggest that BC protects ARPE-19 cells against hypoxia-induced injury through preservation of mitochondrial function and inhibition of ferroptosis.