Sclera as a surrogate marker for determining AGE-modifications in Bruch's membrane using a Raman spectroscopy-based index of aging.
Sclera as a surrogate marker for determining AGE-modifications in Bruch's membrane using a Raman spectroscopy-based index of aging.
复制标题
巩膜作为替代标记，用于使用基于拉曼光谱的衰老指数确定布鲁赫膜中的 AGE 修饰。
DOI：
10.1167/iovs.10-6554
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发表时间：
2011
影响因子：
4.4
通讯作者：
Stitt,AlanW
中科院分区：
文献类型：
--
作者：
Beattie,JRenwick;Pawlak,AnnaM;McGarvey,JohnJ;Stitt,AlanW
目的：拉曼光谱是研究Bruch膜中晚期糖基化终产物（AGEs）的有效探针。然而，因为它是视网膜的最外层，所以这种细胞外基质很难用现有技术在体内分析。巩膜与布鲁赫膜具有许多共同的组成特征，但其更容易用于体内拉曼分析。本研究调查巩膜是否可以作为替代组织，用于基于拉曼光谱的Bruch膜中致病性AGEs的研究。人巩膜和布鲁赫膜解剖死后的眼睛（n= 67）在很宽的年龄范围内（33-92岁），并探测拉曼光谱。从拉曼光谱的数据简化中确定了两种组织的生化组成、AGEs及其与年龄相关的趋势并进行了比较。拉曼显微镜表明，布鲁赫膜和巩膜是由类似范围的生物分子，但不同的相对数量，如血红素/胶原蛋白和弹性蛋白/胶原蛋白的比例。这两种组织积累的AGEs，这些与实际年龄（R2 = 0.824和R2 = 0.717巩膜和布鲁赫膜，分别）。巩膜中AGE加合物的积累速率低于Bruch膜，年龄相关性变化的总体速率较低（Bruch膜的1/4），但随着年龄的增长而显著增加（P< 0.05）。结果表明，巩膜是一个可行的替代标志物，估计年龄积累在布鲁赫膜和可靠地预测实际年龄。这些发现还表明，巩膜可能是未来基于患者的拉曼光谱研究的有用靶组织。
Purpose.: Raman spectroscopy is an effective probe of advanced glycation end products (AGEs) in Bruch's membrane. However, because it is the outermost layer of the retina, this extracellular matrix is difficult to analyze in vivo with current technology. The sclera shares many compositional characteristics with Bruch's membrane, but it is much easier to access for in vivo Raman analysis. This study investigated whether sclera could act as a surrogate tissue for Raman-based investigation of pathogenic AGEs in Bruch's membrane.Methods.: Human sclera and Bruch's membrane were dissected from postmortem eyes (n= 67) across a wide age range (33–92 years) and were probed by Raman spectroscopy. The biochemical composition, AGEs, and their age-related trends were determined from data reduction of the Raman spectra and compared for the two tissues.Results.: Raman microscopy demonstrated that Bruch's membrane and sclera are composed of a similar range of biomolecules but with distinct relative quantities, such as in the heme/collagen and the elastin/collagen ratios. Both tissues accumulated AGEs, and these correlated with chronological age (R 2= 0.824 and R 2= 0.717 for sclera and Bruch's membrane, respectively). The sclera accumulated AGE adducts at a lower rate than Bruch's membrane, and the models of overall age-related changes exhibited a lower rate (one-fourth that of Bruch's membrane) but a significant increase with age (P< 0.05).Conclusions.: The results suggest that the sclera is a viable surrogate marker for estimating AGE accumulation in Bruch's membrane and for reliably predicting chronological age. These findings also suggest that sclera could be a useful target tissue for future patient-based, Raman spectroscopy studies.
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