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Sci Adv ; 5(1): eaau9940, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30662950

RESUMEN

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.


Asunto(s)
Enfermedades Hereditarias del Ojo/metabolismo , Hierro/metabolismo , Hierro/toxicidad , Neuroprotección , Desprendimiento de Retina/metabolismo , Transferrina/metabolismo , Anciano , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Enfermedades Hereditarias del Ojo/cirugía , Femenino , Humanos , Hierro/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Necrosis , Células Fotorreceptoras de Vertebrados/metabolismo , Ratas , Ratas Long-Evans , Ratas Wistar , Retina/metabolismo , Desprendimiento de Retina/cirugía , Epitelio Pigmentado de la Retina/metabolismo , Líquido Subretiniano/metabolismo , Transferrina/genética
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