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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 |
doi: 10.3389/fphar.2025.1543575
This article is part of the Research Topic Insights in Experimental Pharmacology and Drug Discovery: 2024 View all 3 articles
Melatonin protects retinal pigment epithelium cells against ferroptosis in AMD via the PI3K/AKT/MDM2/P53 pathway
Provisionally accepted- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, chongqing, China
Abstract：Oxidative stress-prompted degeneration of the retinal pigment epithelium (RPE) notably contributes to the onset of age-related macular degeneration (AMD). However, the pathways leading to RPE deterioration and possible preventative strategies are not yet completely comprehended. Our research identified that Aβ1-40, a primary variant of Amyloid beta and a significant constituent of drusen, can trigger ferroptosis in RPE.Melatonin, on the other hand, can inhibit the oxidative stress and ferroptosis induced by Aβ1-40 in RPE cells. Melatonin has a protective effect on Aβ1-40-induced AMD, significantly improving the structure of the mouse retina and RPE layer,and facilitating the restoration of visual function. Network pharmacology methods revealed that the potential targets of melatonin for AMD are closely related to ferroptosis. KEGG pathway enrichment analysis indicated that the predominant pathways are significantly associated with the PI3K/AKT/MDM2/P53 signaling pathway.Knocking down the specific expression of MDM2 can significantly weaken the effect of melatonin in inhibiting oxidative stress and ferroptosis. These studies demonstrate that melatonin can suppress cell death by ferroptosis in RPE via the PI3K/AKT/MDM2/P53 pathway, thereby preventing and decelerating the progression of AMD.
Keywords: ferroptosis, Melatonin, Retinal Pigment Epithelium, age-related macular degeneration, Aβ1-40
Received: 11 Dec 2024; Accepted: 21 Jan 2025.
Copyright: © 2025 Wu, Zhao, Du, Lu, He, Shu, Peng and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xing Wang, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, chongqing, China
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