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.
Department of ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
Sci Adv. 2019 Jan 9;5(1):eaau9940. doi: 10.1126/sciadv.aau9940. eCollection 2019 Jan.
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.
在视网膜脱离 (RD) 中，由于视网膜下液 (SRF) 的存在，光感受器与视网膜色素上皮分离，导致光感受器死亡和永久性视力丧失，而成功的手术复位并不能预测完全的视力恢复。由于视网膜铁过载会加剧视网膜疾病中的细胞死亡，我们将铁作为 RD 的预测标志物和治疗靶点进行了评估。在 RD 患者的玻璃体和 SRF 中，我们测量到铁和转铁蛋白 (TF) 饱和度增加，这与视力恢复不良相关。在体外和体内 RD 模型中，铁会引起即刻坏死和延迟凋亡。我们证明 TF 可减少 RD 引起的细胞凋亡和坏死性凋亡，并且通过 RNA 测序，鉴定了介导 TF 的神经保护作用的途径。由于 RD 中会积聚有毒的铁，因此我们提出 TF 补充作为手术的辅助治疗，以改善 RD 患者的视力预后。
