PEDF protects retinal pigment epithelium from ferroptosis and ameliorates dry AMD-like pathology in a murine model.
Geroscience
; 46(2): 2697-2714, 2024 04.
Article
en En
| MEDLINE
| ID: mdl-38153666
ABSTRACT
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.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Serpinas
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Proteínas del Ojo
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Epitelio Pigmentado de la Retina
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Ferroptosis
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Factores de Crecimiento Nervioso
Límite:
Aged
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Animals
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Humans
Idioma:
En
Revista:
Geroscience
Año:
2024
Tipo del documento:
Article
País de afiliación:
China