The Oral Iron Chelator Deferiprone Protects against Iron Overload-Induced Retinal Degeneration
The Oral Iron Chelator Deferiprone Protects against Iron Overload-Induced Retinal Degeneration
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DOI：
10.1167/iovs.10-6207
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发表时间：
2011-02-01
影响因子：
4.4
通讯作者：
Dunaief, Joshua L.
中科院分区：
文献类型：
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作者：
Hadziahmetovic, Majda;Song, Ying;Dunaief, Joshua L.
目的。铁诱导的氧化应激可能会加剧年龄相关性黄斑变性（AMD）。使用具有年龄依赖性视网膜铁积累和AMD的一些特征的铜蓝蛋白/火铁黄蛋白双敲除(DKO)小鼠来测试口服铁螯合剂去铁酮(DFP)对视网膜的保护作用。方法。用 DFP 处理培养的视网膜色素上皮 (ARPE-19) 细胞和小鼠。转铁蛋白受体 mRNA (Tfrc) 是铁水平的指标，通过 qPCR 进行定量。在小鼠中，通过质谱法评估视网膜氧化应激，通过组织学和视网膜电图评估视网膜变性。结果。 60 μM 的 DFP 降低 ARPE-19 细胞中的不稳定铁，增加 Tfrc 并保护 70% 的细胞免受致死剂量的 H2O2 的影响。饮用水中的 DFP 1 mg/mL 在 11 天后使视网膜 Tfrc mRNA 增加了 2.7 倍，并且还增加了转铁蛋白受体蛋白。在 DKO 中，DFP 在 8 个月内将视网膜铁水平降低至未治疗小鼠的 72%，将视网膜氧化应激降低至未治疗水平的 70%，并显着改善视网膜变性。根据组织学和视网膜电图评估，DFP 对野生型 (WT) 或 DKO 小鼠没有视网膜毒性。结论。口服 DFP 对小鼠视网膜没有毒性。它降低了视网膜铁水平和氧化应激，并保护 DKO 小鼠免受铁超载引起的视网膜变性。需要进一步检测 DFP 是否存在涉及氧化应激的视网膜疾病。 （投资眼科可见科学。2011；52：959-968）DOI：10.1167/iovs.10-6207
PURPOSE. Iron-induced oxidative stress may exacerbate age-related macular degeneration (AMD). Ceruloplasmin/Hephaestin double-knockout (DKO) mice with age-dependent retinal iron accumulation and some features of AMD were used to test retinal protection by the oral iron chelator deferiprone (DFP).METHODS. Cultured retinal pigment epithelial (ARPE-19) cells and mice were treated with DFP. Transferrin receptor mRNA (Tfrc), an indicator of iron levels, was quantified by qPCR. In mice, retinal oxidative stress was assessed by mass spectrometry, and degeneration by histology and electroretinography.RESULTS. DFP at 60 mu M decreased labile iron in ARPE-19 cells, increasing Tfrc and protecting 70% of cells against a lethal dose of H2O2. DFP 1 mg/mL in drinking water increased retinal Tfrc mRNA 2.7-fold after 11 days and also increased transferrin receptor protein. In DKOs, DFP over 8 months decreased retinal iron levels to 72% of untreated mice, diminished retinal oxidative stress to 70% of the untreated level, and markedly ameliorated retinal degeneration. DFP was not retina toxic in wild-type (WT) or DKO mice, as assessed by histology and electroretinography.CONCLUSIONS. Oral DFP was not toxic to the mouse retina. It diminished retinal iron levels and oxidative stress and protected DKO mice against iron overload-induced retinal degeneration. Further testing of DFP for retinal disease involving oxidative stress is warranted. (Invest Ophthalmol Vis Sci. 2011;52:959-968) DOI:10.1167/iovs.10-6207