Proanthocyanidins activate Nrf2/GPX4 pathway to inhibit ferroptosis and exert protective effects on dry ARMD
10.3980/j.issn.1672-5123.2026.7.03
- VernacularTitle:原花青素激活Nrf2/GPX4途径抑制铁死亡及其对干性ARMD的保护作用
- Author:
Chuan FENG
1
;
Zhong TANG
1
Author Information
1. Optometry Teaching and Research Section, School of Medical Technology, Yongzhou Vocational Technical College, Yongzhou 425000, Hunan Province, China
- Publication Type:Journal Article
- Keywords:
dry age-related macular degeneration(ARMD);
proanthocyanidins;
Nrf2;
GPX4;
ferroptosis
- From:
International Eye Science
2026;26(7):1116-1126
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate whether proanthocyanidins(PAC)can ameliorate ferroptosis in retinal pigment epithelium(RPE)cells via the Nrf2/GPX4 pathway, and to evaluate its protective effect in dry age-related macular degeneration(ARMD). METHODS: The protective effects of PAC against ferroptosis were evaluated using an in vitro model of H2O2-stimulated human RPE cells(ARPE-19)and an in vivo dry ARMD animal model induced by sodium iodate(NaIO3). CCK-8 assay was applied to assess cell viability. Calcein-AM/PI staining was applied to determine the level of cell death. Lipid peroxidation(LPO)levels were measured using a lipid peroxidation assay kit. CM-H2DCFDA was used to detect the level of reactive oxygen species(ROS)in cells. MitoSOX probe was employed to measure the mitochondrial ROS level. JC-1 staining was used to evaluate the changes in mitochondrial membrane potential. Western Blot was performed to detect the expression levels of proteins(Nrf2, GPX4, and HO-1)related to the Nrf2 pathway. Retinal flat mounts were used to evaluate the structure and function of RPE. Hematoxylin and eosin(H & E)staining was applied to assess the morphological changes in rat retinas. Rhodopsin and opsin staining was used to evaluate visual function in the retina. TUNEL staining was employed to detect apoptosis in retinal cells. RESULTS: H2O2 exacerbates ferroptosis in ARPE-19 cells, as evidenced by elevated levels of Fe2+, ROS, and LPO. PAC preconditioning ameliorates mitochondrial function, reduces intracellular Fe2+, ROS, and LPO levels, and suppresses ferroptosis in RPE cells via activation of the Nrf2/GPX4 signaling pathway. In a NaIO3-induced dry ARMD model, both PAC and the ferroptosis inhibitor Fer-1 reverse the downregulation of retinal Nrf2/GPX4 expression and attenuate retinal cell death.CONCLUSION:PAC inhibits ferroptosis via the Nrf2/GPX4 pathway, offering a novel potential therapeutic strategy for retinal degeneration.
