Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.

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Version: Final published version
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Serval ID
serval:BIB_66A0081D7AD0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.
Journal
Science advances
Author(s)
Daruich A., Le Rouzic Q., Jonet L., Naud M.C., Kowalczuk L., Pournaras J.A., Boatright J.H., Thomas A., Turck N., Moulin A., Behar-Cohen F., Picard E.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
01/2019
Peer-reviewed
Oui
Volume
5
Number
1
Pages
eaau9940
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Aged, Animals, Apoptosis/drug effects, Disease Models, Animal, Eye Diseases, Hereditary/metabolism, Eye Diseases, Hereditary/surgery, Female, Humans, Iron/metabolism, Iron/pharmacology, Iron/toxicity, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Necrosis, Neuroprotection, Photoreceptor Cells, Vertebrate/metabolism, Rats, Rats, Long-Evans, Rats, Wistar, Retina/metabolism, Retinal Detachment/metabolism, Retinal Detachment/surgery, Retinal Pigment Epithelium/metabolism, Subretinal Fluid/metabolism, Transferrin/genetics, Transferrin/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2019 15:00
Last modification date
21/11/2022 8:07
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