Hahn Paul, Milam Ann H, Dunaief Joshua L
F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Arch Ophthalmol. 2003 Aug;121(8):1099-105. doi: 10.1001/archopht.121.8.1099.
To investigate whether iron is involved in the pathogenesis of age-related macular degeneration (AMD).
Postmortem AMD-affected (nonexudative or exudative) and healthy maculas were studied using the 3,3'-diaminobenzidine-enhanced Perls Prussian blue stain. The Perls Prussian blue stain was quantified by computer-assisted analysis of digital images. To determine whether the iron was chelatable, sections treated with the iron chelator deferoxamine were compared with adjacent, nonchelated sections.
Compared with healthy maculas, AMD-affected maculas had statistically significant increases in the total iron level. Some of this iron was chelatable. The iron was present in retinal pigment epithelium and Bruch's membrane in maculas from patients who had drusen only, geographic atrophy, and exudative AMD in pathologic areas and, occasionally, in relatively healthy areas.
Oxidative stress has been implicated in the pathogenesis of AMD by the Age-Related Eye Disease Study. Increased concentrations of iron, which generate highly reactive hydroxyl radicals via the Fenton reaction, may induce oxidative stress in the macula and lead to AMD. As the increased iron concentrations in AMD-affected eyes consist in part of a chelatable iron pool, treatment of patients who have AMD with iron chelators might be considered a potential therapy. While there are, as yet, no clinical data indicating that the treatment of patients who have AMD with iron chelators is beneficial, data presented herein indicate that further investigation of iron concentrations in postmortem tissues and the mechanisms of iron transport in the retina is warranted.
研究铁是否参与年龄相关性黄斑变性（AMD）的发病机制。
使用3,3'-二氨基联苯胺增强的普鲁士蓝染色法对死后受AMD影响（非渗出性或渗出性）的黄斑和健康黄斑进行研究。通过计算机辅助分析数字图像对普鲁士蓝染色进行定量。为了确定铁是否可螯合，将用铁螯合剂去铁胺处理的切片与相邻的未螯合切片进行比较。
与健康黄斑相比，受AMD影响的黄斑总铁水平有统计学意义的升高。其中一些铁是可螯合的。在仅患有玻璃膜疣、地图样萎缩和渗出性AMD患者的黄斑的视网膜色素上皮和 Bruch 膜中，在病理区域以及偶尔在相对健康的区域中存在铁。
年龄相关性眼病研究表明氧化应激与AMD的发病机制有关。通过芬顿反应产生高活性羟基自由基的铁浓度增加，可能会在黄斑中诱导氧化应激并导致AMD。由于受AMD影响的眼睛中铁浓度升高部分由可螯合铁池组成，因此可以考虑用铁螯合剂治疗AMD患者作为一种潜在的治疗方法。虽然目前尚无临床数据表明用铁螯合剂治疗AMD患者有益，但本文提供的数据表明有必要进一步研究死后组织中的铁浓度以及视网膜中铁转运的机制。
