Format

Send to

Choose Destination
Sci Adv. 2019 Jan 9;5(1):eaau9940. doi: 10.1126/sciadv.aau9940. eCollection 2019 Jan.

Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.

Author information

1
INSERM, UMRS1138, Team 17, From physiopathology of ocular diseases to clinical development, Université Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
2
Department of ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
3
Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris, France.
4
Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA, USA.
5
Center of Excellence, Atlanta Veterans Administration Medical Center, Decatur, GA, USA.
6
Geneva University Hospitals, Unit of Toxicology, CURML, Geneva, Switzerland.
7
Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, 1011 Lausanne, Switzerland.
8
Geneva University, Department of Human Protein Science, Geneva, Switzerland.
9
Ophtalmopole, Cochin Hospital, AP-HP, Assistance Publique Hôpitaux de Paris, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.

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.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center