Salvianolic acid a attenuates sodium iodate-induced ferroptosis in age-related macular degeneration models via the SLC7A11/GPX4 axis.

INTRODUCTION

Oxidative stress-mediated retinal pigment epithelial (RPE) cell injury is a key pathological feature of age-related macular degeneration (AMD). Ferroptosis-an iron-dependent form of regulated cell death driven by lipid peroxidation-has been increasingly identified as a critical executor of RPE degeneration and a key pathogenic mechanism in AMD. This study aimed to investigate the mechanism by which Salvianolic acid A (SalA) alleviates ferroptosis in RPE cells under sodium iodate (NaIO3)-induced damage.

METHODS

Using in vitro (ARPE-19 cells) and in vivo (mice) NaIO3-induced injury models. We assessed cell viability, ferroptosis markers (iron, lipid peroxidation, glutathione), mitochondrial ultrastructure, and key protein expression via biochemical assays, flow cytometry, transmission electron microscopy, and Western blotting.

RESULTS

SalA pretreatment effectively mitigated NaIO3-induced ferroptosis, reducing lipid peroxidation, iron overload, and mitochondrial damage. Mechanistically, SalA upregulated the key ferroptosis regulators SLC7A11 and GPX4. Critically, this protection was significantly attenuated by the SLC7A11 inhibitor erastin, confirming the essential role of this axis. In mice, SalA attenuated NaIO3-induced retinal structural damage and enhanced SLC7A11/GPX4 expression in retina tissues.

CONCLUSION

This study identifies SalA as a potent inhibitor of ferroptosis in RPE cells, primarily through activation of the SLC7A11/GPX4 axis. These findings suggest that SalA may hold therapeutic potential for AMD and provide a preliminary pharmacological basis for further exploration in retinal degenerative diseases.