Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States.
Arch Biochem Biophys. 2013 Nov 15;539(2):196-202. doi: 10.1016/j.abb.2013.08.005. Epub 2013 Aug 19.
The accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been implicated in the development of age-related macular degeneration (AMD) in humans. The exact composition of lipofuscin is not known but its best characterized component is N-retinylidene-N-retinylethanolamine (A2E), a byproduct of the retinoid visual cycle. Utilizing our recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS)-based technique to determine the spatial distribution of A2E, this study compares the relationships of lipofuscin fluorescence and A2E in the murine and human RPE on representative normal tissue. To identify molecules with similar spatial patterns, the images of A2E and lipofuscin were correlated with all the individual images in the MALDI-IMS dataset. In the murine RPE, there was a remarkable correlation between A2E and lipofuscin. In the human RPE, however, minimal correlation was detected. These results were reflected in the marked distinctions between the molecules that spatially correlated with the images of lipofuscin and A2E in the human RPE. While the distribution of murine lipofuscin showed highest similarities with some of the known A2E-adducts, the composition of human lipofuscin was significantly different. These results indicate that A2E metabolism may be altered in the human compared to the murine RPE.
脂褐素在视网膜色素上皮 (RPE) 中的积累与人类年龄相关性黄斑变性 (AMD) 的发展有关。脂褐素的确切成分尚不清楚，但它最具特征的成分是 N-视黄基-N-视黄醇乙胺 (A2E)，这是视黄醛视觉循环的副产物。本研究利用我们最近开发的基于基质辅助激光解吸/电离成像质谱 (MALDI-IMS) 的技术来确定 A2E 在小鼠和人 RPE 中的空间分布，以比较正常组织中脂褐素荧光和 A2E 的关系。为了识别具有相似空间模式的分子，将 A2E 和脂褐素的图像与 MALDI-IMS 数据集中的所有单个图像进行相关。在小鼠 RPE 中，A2E 和脂褐素之间存在显著相关性。然而，在人 RPE 中，检测到最小的相关性。这些结果反映在与人类 RPE 中脂褐素和 A2E 的图像具有空间相关性的分子之间的明显区别。虽然小鼠脂褐素的分布与一些已知的 A2E 加合物具有最高的相似性，但人类脂褐素的组成明显不同。这些结果表明，与小鼠 RPE 相比，A2E 代谢可能在人类中发生改变。
