Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection

• Authors: Alejandra Daruich, Universite Sorbonne Paris Cite; Quentin Le Rouzic, Universite Sorbonne Paris Cite; Laurent Jonet, Universite Sorbonne Paris Cite; Marie-Christine Naud, Universite Sorbonne Paris Cite; Laura Kowalczuk, University of Lausanne; Jean-Antoine Pournaras, University of Lausanne; Jeffrey Boatright, Emory University; Aurelien Thomas, Geneva University Hospitals; Natacha Turck, University of Lausanne; Alexandre Moulin, University of Lausanne; Francine Behar-Cohen, Universite Sorbonne Paris Cite; Emilie Picard, Universite Sorbonne Paris Cite
• Journal Title: Science Advances
• Volume: Volume 5, Number 1
• Publisher: American Association for the Advancement of Science: Science Advances | 2019-01-01, Pages eaau9940-eaau9940
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1126/sciadv.aau9940
• Subjects: Health Sciences, Opthamology; Health Sciences, Toxicology; Biology, Physiology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; PHOTORECEPTOR CELL-DEATH; GROWTH-FACTOR; PROTEIN; TOXICITY; DEGENERATION; DELIVERY; IGFBP-3; CANCER

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.