Melatonin Alleviates Retinal Ischemia–Reperfusion Injury by Inhibiting p53–Mediated Ferroptosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Human Eye Tissue Subject Study
2.2. Experimental Design and Drug Administration
2.3. Mouse RIR Injury Model
2.4. Histological Analysis of Retinal Tissue and Retinal Ganglion Cell (RGC) Survival Analysis
2.5. Spectral Domain Optical Coherence Tomography (OCT) Imaging of Live–Mouse Retinas
2.6. Primary RGC Culture and Treatment
2.7. Cell Viability Assay
2.8. Cell Death Assay
2.9. Real–Time Polymerase Chain Reaction (qRT–PCR)
2.10. Western Blot Analysis
2.11. Measurement of Iron, Malondialdehyde (MDA), and Glutathione (GSH) Levels in Retinal Tissue Samples
2.12. Immunohistochemical, Immunofluorescence Staining, and TUNEL Assay
2.13. Analysis of the Mitochondrial Membrane Potential (MMP) via JC–1 Staining
2.14. Transmission Electron Microscopy (TEM)
2.15. Measurement of Lipid Peroxidation In Vitro
2.16. ChIP–PCR Assay
2.17. Coimmunoprecipitation (Co–IP) Assay
2.18. Statistical Analysis
3. Results
3.1. Significant RGC Loss and the Expression of Ferroptosis Markers in Enucleated Eyes from Glaucoma Patients
3.2. Fer–1 Pretreatment Attenuated RIR–Induced Retinal Damage
3.3. MT Pretreatment Attenuated Retinal Damage after RIR
3.4. Melatonin Attenuated RIR–Induced Ferroptosis
3.5. MT Promoted Primary Cultured RGC Survival, Restored MMP, and Inhibited Lipid Peroxidation following OGD/R
3.6. MT Alleviated RGC Apoptosis Induced by RIR Injury
3.7. MT Ameliorated Reactive Gliosis and the Inflammatory Response after RIR Injury
3.8. The Protective Effect of MT against RIR Injury through MT Receptors
3.9. MT Pretreatment Attenuated RIR–Induced Ferroptosis by Mediating the p53/Slc7a11/Alox12 Axis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Zhang, F.; Lin, B.; Huang, S.; Wu, P.; Zhou, M.; Zhao, J.; Hei, X.; Ke, Y.; Zhang, Y.; Huang, D. Melatonin Alleviates Retinal Ischemia–Reperfusion Injury by Inhibiting p53–Mediated Ferroptosis. Antioxidants 2023, 12, 1173. https://doi.org/10.3390/antiox12061173
Zhang F, Lin B, Huang S, Wu P, Zhou M, Zhao J, Hei X, Ke Y, Zhang Y, Huang D. Melatonin Alleviates Retinal Ischemia–Reperfusion Injury by Inhibiting p53–Mediated Ferroptosis. Antioxidants. 2023; 12(6):1173. https://doi.org/10.3390/antiox12061173
Chicago/Turabian StyleZhang, Fan, Bingying Lin, Siyu Huang, Pengsen Wu, Min Zhou, Jing Zhao, Xiangqing Hei, Yu Ke, Yiting Zhang, and Danping Huang. 2023. "Melatonin Alleviates Retinal Ischemia–Reperfusion Injury by Inhibiting p53–Mediated Ferroptosis" Antioxidants 12, no. 6: 1173. https://doi.org/10.3390/antiox12061173
APA StyleZhang, F., Lin, B., Huang, S., Wu, P., Zhou, M., Zhao, J., Hei, X., Ke, Y., Zhang, Y., & Huang, D. (2023). Melatonin Alleviates Retinal Ischemia–Reperfusion Injury by Inhibiting p53–Mediated Ferroptosis. Antioxidants, 12(6), 1173. https://doi.org/10.3390/antiox12061173