Lack of Correlation Between the Spatial Distribution of A2E and Lipofuscin Fluorescence in the Human Retinal Pigment Epithelium
Lack of Correlation Between the Spatial Distribution of A2E and Lipofuscin Fluorescence in the Human Retinal Pigment Epithelium
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DOI：
10.1167/iovs.13-12250
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发表时间：
2013-08-01
影响因子：
4.4
通讯作者：
Crouch, Rosalie K.
中科院分区：
文献类型：
--
作者：
Ablonczy, Zsolt;Higbee, Daniel;Crouch, Rosalie K.
目的。RPE中脂褐素的积累是眼睛老化的标志。脂褐素最具特征的成分是A2E，它是正常类维甲酸视觉周期的双类维甲酸副产物，在体外表现出广谱的细胞毒性作用。本研究的目的是研究脂褐素和A2E在人rpe中的分布。脂褐素荧光在来自不同年龄的人类供体的平板RPE中成像。采用基质辅助激光解吸-电离成像质谱法（MALDI-IMS）测定了A2E及其氧化物在平板RPE组织切片和视网膜横切面上的空间分布。我们的数据支持临床观察的强RPE荧光，随年龄增加，在RPE的中心区域。然而，A2E的分布与脂褐素之间没有相关性，因为A2E的水平在远周最高，向中心区域降低。视网膜横截面的高分辨率MALDI-IMS证实了在RPE平板支架上获得的A2E定位数据。单氧化和双氧化A2E的分布与A2E相似，但有代表性
PURPOSE. The accumulation of lipofuscin in the RPE is a hallmark of aging in the eye. The best characterized component of lipofuscin is A2E, a bis-retinoid byproduct of the normal retinoid visual cycle, which exhibits a broad spectrum of cytotoxic effects in vitro. The purpose of our study was to correlate the distribution of lipofuscin and A2E across the human RPE.METHODS. Lipofuscin fluorescence was imaged in flat-mounted RPE from human donors of various ages. The spatial distributions of A2E and its oxides were determined using matrix-assisted laser desorption-ionization imaging mass spectrometry (MALDI-IMS) on flat-mounted RPE tissue sections and retinal cross-sections.RESULTS. Our data support the clinical observations of strong RPE fluorescence, increasing with age, in the central area of the RPE. However, there was no correlation between the distribution of A2E and lipofuscin, as the levels of A2E were highest in the far periphery and decreased toward the central region. High-resolution MALDI-IMS of retinal cross-sections confirmed the A2E localization data obtained in RPE flat-mounts. Singly-and doubly-oxidized A2E had distributions similar to A2E, but represented