PCSK7, a potential target for the treatment of age-related macular degeneration: inhibition of retinal epithelial cell death

AIM Age-related macular degeneration (AMD) is a complex disease whose pathophysiology is not fully understood. Hence, the purpose of this study was to investigate the specific manifestations of PCSK7 in retinal epithelial cells. METHODS Lentiviral vectors overexpressing PCSK7 were infected into H ₂ O ₂ -treated ARPE-19 cells to investigate the mechanism of action. WB and RT-qPCR were used to analyze the overexpression efficiency. Then, CCK8 assay was used to investigate the proliferation of ARPE-19 cells, while flow cytometry and immunofluorescence were used to study the apoptosis. Iron accumulation and GSH content in cells were determined by ELISA and WB was used to determine the expression of anti-ferroptosis protein. Finally, JC-1 staining was used to investigate cellular mitochondrial membrane potential. RESULTS Overexpressing PCSK7 enhanced the proliferation and inhibited the apoptosis of ARPE-19 cells treated with H ₂ O ₂ . Meanwhile, Increased PCSK7 expression suppressed intracellular iron levels and GSH content and inhibited the ferroptosis process. In addition, overexpression of PCSK7 restored mitochondrial membrane potential, thereby alleviating H ₂ O ₂ -induced mitochondrial damage. CONCLUSION PCSK7 might be one of the targets for the treatment of AMD through the regulation of retinal epithelial cell death.