PEDF protects retinal pigment epithelium from ferroptosis and ameliorates dry AMD-like pathology in a murine model.
Age-related macular degeneration
Ferroptosis
Pigment epithelial-derived factor
Retinal pigment epithelium
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
28 Dec 2023
28 Dec 2023
Historique:
received:
06
06
2023
accepted:
05
12
2023
medline:
28
12
2023
pubmed:
28
12
2023
entrez:
28
12
2023
Statut:
aheadofprint
Résumé
Age-related macular degeneration (AMD) is the leading cause of irreversible vision damage among elderly individuals. There is still no efficient treatment for dry AMD. Retinal pigment epithelial (RPE) degeneration has been confirmed to play an important role in dry AMD. Recent studies have reported that ferroptosis caused by iron overload and lipid peroxidation may be the primary causes of RPE degeneration. However, the upstream regulatory molecules of RPE ferroptosis remain largely unknown. Pigment epithelium-derived factor (PEDF) is an important endogenic protective factor for the RPE. Our results showed that in the murine dry AMD model induced by sodium iodate (SI), PEDF expression was downregulated. Moreover, dry AMD-like pathology was observed in PEDF-knockout mice. Therefore, the aim of this study was to reveal the effects and mechanism of PEDF on RPE ferroptosis and investigate potential therapeutic targets for dry AMD. The results of lipid peroxidation and transmission electron microscope showed that retinal ferroptosis was significantly activated in SI-treated mice and PEDF-knockout mice. Restoration of PEDF expression ameliorated SI-induced retinal dysfunction in mice, as assessed by electroretinography and optical coherence tomography. Mechanistically, western blotting and immunofluorescence analysis demonstrated that the overexpression of PEDF could upregulate the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain-1 (FTH1), which proved to inhibit lipid peroxidation and RPE ferroptosis induced by SI. This study revealed the novel role of PEDF in ferroptosis inhibition and indicated that PEDF might be a potential therapeutic target for dry AMD.
Identifiants
pubmed: 38153666
doi: 10.1007/s11357-023-01038-3
pii: 10.1007/s11357-023-01038-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 82171066
Organisme : Guangzhou Science and Technology Plan Project
ID : 202102010333
Organisme : Guangzhou Science and Technology Plan Project
ID : SL2024A03J00359
Organisme : Guangdong Basic and Applied Basic Research Fund Project
ID : 2021A1515010895
Organisme : Guangdong Basic and Applied Basic Research Fund Project
ID : SL2023A04J00138
Informations de copyright
© 2023. The Author(s), under exclusive licence to American Aging Association.
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