Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.
Aged
Animals
Apoptosis
/ drug effects
Disease Models, Animal
Eye Diseases, Hereditary
/ metabolism
Female
Humans
Iron
/ metabolism
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 Pigment Epithelium
/ metabolism
Subretinal Fluid
/ metabolism
Transferrin
/ genetics
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
03
08
2018
accepted:
28
11
2018
entrez:
22
1
2019
pubmed:
22
1
2019
medline:
9
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30662950
doi: 10.1126/sciadv.aau9940
pii: aau9940
pmc: PMC6326753
doi:
Substances chimiques
Transferrin
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaau9940Subventions
Organisme : NEI NIH HHS
ID : R01 EY028859
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY006360
Pays : United States
Organisme : RRD VA
ID : I21 RX001924
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY021592
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY028450
Pays : United States
Organisme : RRD VA
ID : I01 RX002806
Pays : United States
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