Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection

被引：53

作者：

Daruich, Alejandra ^{[1
,2
,3
]}

Le Rouzic, Quentin ^{[1
]}

Jonet, Laurent ^{[1
]}

Naud, Marie-Christine ^{[1
]}

Kowalczuk, Laura ^{[2
]}

Pournaras, Jean-Antoine ^{[2
]}

Boatright, Jeffrey H. ^{[4
,5
]}

Thomas, Aurelien ^{[6
,7
]}

Turck, Natacha ^{[7
,8
]}

Moulin, Alexandre ^{[2
]}

Behar-Cohen, Francine ^{[1
,7
,9
]}

Picard, Emilie ^{[1
]}

机构：

[1] Univ Sorbonne Paris Cite, INSERM, UMRS1138, Team 17,Physiopathol Ocular Dis Clin Dev,Ctr Rech, 15 Rue Ecole Med, F-75006 Paris, France

[2] Univ Lausanne, Jules Gonin Eye Hosp, Fdn Asile Aveugles, Dept Ophthalmol, Lausanne, Switzerland

[3] Necker Enfants Malades Univ Hosp, AP HP, Ophthalmol Dept, Paris, France

[4] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA

[5] Atlanta Vet Adm Med Ctr, Ctr Excellence, Decatur, GA USA

[6] Geneva Univ Hosp, Toxicol Unit, CURML, Geneva, Switzerland

[7] Univ Lausanne, Fac Biol & Med, Rue Bugnon 21, CH-1011 Lausanne, Switzerland

[8] Univ Geneva, Dept Human Prot Sci, Geneva, Switzerland

[9] Cochin Hosp, AP HP, Ophtalmopole, 24 Rue Faubourg St Jacques, F-75014 Paris, France

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 01期

关键词：

PHOTORECEPTOR CELL-DEATH; GROWTH-FACTOR; OXIDATIVE STRESS; PROTEIN; TOXICITY; DEGENERATION; DELIVERY; IGFBP-3; CANCER;

D O I：

10.1126/sciadv.aau9940

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 44 条

[1]

ANDERSON DH, 1983, INVEST OPHTH VIS SCI, V24, P906

[2] Conditional Muller Cell Ablation Leads to Retinal Iron Accumulation [J].