Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection

In retinal detachment (RD), photoreceptor death and permanent vision loss are caused by neurosensory retina separating from the retinal pigment epithelium because of subretinal fluid (SRF), and successful surgical reattachment is not predictive of total visual recovery. As retinal iron overload exac...

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Bibliographic Details
Published in:Science advances 2019-01, Vol.5 (1), p.eaau9940-eaau9940
Main Authors: Daruich, Alejandra, Le Rouzic, Quentin, Jonet, Laurent, Naud, Marie-Christine, Kowalczuk, Laura, Pournaras, Jean-Antoine, Boatright, Jeffrey H, Thomas, Aurélien, Turck, Natacha, Moulin, Alexandre, Behar-Cohen, Francine, Picard, Emilie
Format: Article
Language:English
Subjects:
Aged
Animals
Apoptosis
Apoptosis - drug effects
Biochemistry, Molecular Biology
Disease Models, Animal
Eye Diseases, Hereditary
Eye Diseases, Hereditary - metabolism
Eye Diseases, Hereditary - surgery
Female
Humans
Iron
Iron - metabolism
Iron - pharmacology
Iron - toxicity
Life Sciences
Mice
Mice, Inbred C57BL
Mice, Transgenic
Middle Aged
Necrosis
Neuroprotection
Neuroscience
Photoreceptor Cells, Vertebrate
Photoreceptor Cells, Vertebrate - metabolism
Rats
Rats, Long-Evans
Rats, Wistar
Retina
Retina - metabolism
Retinal Detachment
Retinal Detachment - metabolism
Retinal Detachment - surgery
Retinal Pigment Epithelium
Retinal Pigment Epithelium - metabolism
SciAdv r-articles
Subretinal Fluid
Subretinal Fluid - metabolism
Transferrin
Transferrin - genetics
Transferrin - metabolism
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Summary:In retinal detachment (RD), photoreceptor death and permanent vision loss are caused by neurosensory retina separating from the retinal pigment epithelium because of subretinal fluid (SRF), and successful surgical reattachment is not predictive of total visual recovery. As retinal iron overload exacerbates cell death in retinal diseases, we assessed iron as a predictive marker and therapeutic target for RD. In the vitreous and SRF from patients with RD, we measured increased iron and transferrin (TF) saturation that is correlated with poor visual recovery. In ex vivo and in vivo RD models, iron induces immediate necrosis and delayed apoptosis. We demonstrate that TF decreases both apoptosis and necroptosis induced by RD, and using RNA sequencing, pathways mediating the neuroprotective effects of TF are identified. Since toxic iron accumulates in RD, we propose TF supplementation as an adjunctive therapy to surgery for improving the visual outcomes of patients with RD.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aau9940