Adler Leopold, Boyer Nicholas P, Anderson David M, Spraggins Jeffrey M, Schey Kevin L, Hanneken Anne, Ablonczy Zsolt, Crouch Rosalie K, Koutalos Yiannis
Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA.
Mass Spectrometry Research Center, Vanderbilt School of Medicine, Nashville, TN, USA.
Photochem Photobiol Sci. 2015 Nov;14(11):1983-90. doi: 10.1039/c5pp00156k.
The bis-retinoid N-retinylidene-N-retinylethanolamine (A2E) is one of the major components of lipofuscin, a fluorescent material that accumulates with age in the lysosomes of the retinal pigment epithelium (RPE) of the human eye. Lipofuscin, as well as A2E, exhibit a range of cytotoxic properties, which are thought to contribute to the pathogenesis of degenerative diseases of the retina such as Age-related Macular Degeneration. Consistent with such a pathogenic role, high levels of lipofuscin fluorescence are found in the central area of the human RPE, and decline toward the periphery. Recent reports have however suggested a surprising incongruence between the distributions of lipofuscin and A2E in the human RPE, with A2E levels being lowest in the central area and increasing toward the periphery. To appraise such a possibility, we have quantified the levels of A2E in the central and peripheral RPE areas of 10 eyes from 6 human donors (ages 75-91 years) with HPLC and UV/VIS spectroscopy. The levels of A2E in the central area were on average 3-6 times lower than in peripheral areas of the same eye. Furthermore, continuous accumulation of selected ions (CASI) imaging mass spectrometry showed the presence of A2E in the central RPE, and at lower intensities than in the periphery. We have therefore corroborated that in human RPE the levels of A2E are lower in the central area compared to the periphery. We conclude that the levels of A2E cannot by themselves provide an explanation for the higher lipofuscin fluorescence found in the central area of the human RPE.
双视黄醛N-视黄叉-N-视黄基乙醇胺（A2E）是脂褐素的主要成分之一，脂褐素是一种荧光物质，随着年龄增长在人眼视网膜色素上皮（RPE）的溶酶体中积累。脂褐素以及A2E都表现出一系列细胞毒性特性，这些特性被认为与视网膜退行性疾病如年龄相关性黄斑变性的发病机制有关。与这种致病作用一致，在人RPE的中心区域发现高水平的脂褐素荧光，并向周边逐渐降低。然而，最近的报告表明，在人RPE中脂褐素和A2E的分布之间存在惊人的不一致，A2E水平在中心区域最低，并向周边增加。为了评估这种可能性，我们使用高效液相色谱法（HPLC）和紫外/可见光谱法对6名人类供体（年龄75 - 91岁）的10只眼睛的中心和周边RPE区域中的A2E水平进行了定量。中心区域的A2E水平平均比同一只眼睛的周边区域低3 - 6倍。此外，选定离子连续积累（CASI）成像质谱显示中心RPE中存在A2E，且强度低于周边区域。因此，我们证实了在人RPE中，中心区域的A2E水平低于周边区域。我们得出结论，A2E的水平本身不能解释在人RPE中心区域发现的较高脂褐素荧光。
