Int J Clin Exp Pathol. 2024 Oct 15;17(10):371-380. doi: 10.62347/LEHU9944. eCollection 2024.
ABSTRACT
BACKGROUND: Age-related macular degeneration (AMD) is a complex disease with a pathophysiology that remains incompletely understood. PCSK7 is closely related to the normal development of ocular tissues; however, the roles and mechanisms of PCSK7 in AMD have yet to be elucidated. Therefore, the purpose of this study was to investigate the specific manifestations of PCSK7 in AMD.
METHODS: An AMD cell model was established by using hydrogen peroxide (H2O2)-treated ARPE-19 cells. The efficiency of PCSK7 overexpression was analyzed by western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR). Subsequently, a Cell Counting Kit 8 (CCK-8) assay was employed to assess the proliferation of ARPE-19 cells, while flow cytometry and immunofluorescence were utilized to examine apoptosis. Iron accumulation and glutathione (GSH) levels in cells were measured using Enzyme-linked immunosorbent assay (ELISA), and WB was conducted to evaluate the expression of anti-ferroptosis protein. Finally, JC-1 staining was performed to assess mitochondrial membrane potential.
RESULTS: Overexpressing of PCSK7 enhanced the proliferation and inhibited the apoptosis of ARPE-19 cells treated with H2O2. Additionally, increased PCSK7 expression suppressed intracellular iron levels and GSH content, thereby inhibiting the ferroptosis process. Furthermore, overexpression of PCSK7 restored mitochondrial membrane potential, alleviating H2O2-induced mitochondrial damage.
CONCLUSIONS: PCSK7 might be one of the targets for the treatment of AMD through the regulation of retinal epithelial cell death.
PMID:39544716 | PMC:PMC11558318 | DOI:10.62347/LEHU9944