serval:BIB_66A0081D7AD0
Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.
10.1126/sciadv.aau9940
000457547900026
30662950
Daruich
A.
author
Le Rouzic
Q.
author
Jonet
L.
author
Naud
M.C.
author
Kowalczuk
L.
author
Pournaras
J.A.
author
Boatright
J.H.
author
Thomas
A.
author
Turck
N.
author
Moulin
A.
author
Behar-Cohen
F.
author
Picard
E.
author
article
2019-01
Science advances
2375-2548
2375-2548
journal
5
1
eaau9940
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.
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
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
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