Conclusion
These findings suggest targeting ferroptosis may be a novel strategy for the management of retinal degeneration. Puerarin may exert some of its ocular benefits by attenuating ferroptosis.
Results
Models of iron overload in Kunming mice, 661W cell, and ARPE-19 cell are established. Increased iron deposition significantly worsens retinal pathology, decreases cell viability, and induces ferroptotic changes. Puerarin mitigates iron overload-induced ferroptosis by decreasing excessive iron through the regulation of iron handling proteins and lowering lipid peroxidation through the inhibition of cyclooxygenase 2 expression and activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and downstream ferroptosis-related proteins (solute carrier family 7 member 11, glutathione peroxidase 4 and heme oxygenase-1). The protective effect of puerarin on ferroptosis is diminished by the Nrf2-specific inhibitor ML385.