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首页> 外文期刊>Journal of mass spectrometry: JMS >Compositional studies of human RPE lipofuscin
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Compositional studies of human RPE lipofuscin

机译：人RPE脂褐素的组成研究

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Age-related macular degeneration (AMD) is an ocular disease that causes visual loss and legal blindness in the elderly population. The etiology of AMD is complex and may include genetic predispositions, accumulation of lipofuscin and drusen, local inflammation and neovascularization. The accumulation of lipofuscin has been shown to precede the death of photoreceptor cells and the deterioration of the RPE. As a result, the determination of the photosensitive components of lipofuscin has been of major interest. One of these components, previously identified as a bis-retinoid pyridinium compound, is referred to as A2E. A2E has been characterized by mass spectrometry and is known to have a mass of 592 Da. Most remaining chromophores in RPE lipofuscin are structurally related to A2E as determined by their fragmentation pattern with losses of M ± 190, 174 and/or 150 Da. Analysis of lipofuscin from various donors indicated that the extracts consist of as many as 15 of these hydrophobic components, which are also observed to form spontaneously in vitro over extended periods of time. These consist of ca 90% of the A2E-like components in RPE lipofuscin and correspond to derivatized A2E with discrete molecular weights of 800–900 m/z, 970–1080 m/z and above 1200 m/z regions. It was determined that these species are formed from self-reaction of A2E oxidation products or their reaction with A2E itself to form higher molecular weight products. The majority of modifications are much more hydrophobic than A2E and exhibit increasingly higher values of log P. This acts as a driving force for the sequestering of A2E into granules resulting in a concomitant diminution of its reactivity in vivo.
机译：与年龄有关的黄斑变性（AMD）是一种眼病，可导致老年人口视力丧失和法律失明。 AMD的病因很复杂，可能包括遗传易感性，脂褐素和玻璃疣的积聚，局部炎症和新血管形成。脂褐素的积累已显示在感光细胞死亡和RPE恶化之前。结果，脂褐素的光敏组分的测定已引起人们的极大兴趣。这些成分之一，以前被确定为双类视黄醇吡啶鎓化合物，被称为A2E。 A2E已通过质谱表征，已知质量为592 Da。 RPE脂褐素中大多数剩余的发色团在结构上与A2E有关，这取决于它们的断裂模式，其损失为M±190、174和/或150 Da。对来自各种供体的脂褐素的分析表明，提取物由多达15种这些疏水性成分组成，并且还观察到它们在体外会在很长一段时间内自发形成。它们由RPE脂褐素中大约90％的A2E样成分组成，对应于离散分子量为800–900 m / z，970–1080 m / z和1200 m / z以上区域的衍生化A2E。已确定这些物质是由A2E氧化产物的自反应或与A2E本身反应形成较高分子量的产物形成的。大多数修饰比A2E疏水得多，并显示出越来越高的log P值。这是将A2E螯合成颗粒的驱动力，导致其体内反应性随之降低。

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