High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins
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DOI:
10.1007/s13361-015-1143-9
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发表时间:
2015-06-01
影响因子:
3.2
通讯作者:
Schey, Kevin L.
Schey, Kevin L.
中科院分区:
化学3区
文献类型:
--
作者:
Anderson, David M. G.;Spraggins, Jeffrey M.;Schey, Kevin L.

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人类视神经将信号从视网膜传递到大脑的视觉皮层。每根视神经由大约一百万根神经纤维组成,这些神经纤维被组织成800-1200根纤维的束,由结缔组织和支持性胶质细胞包围。视神经损伤会导致许多致盲疾病,包括:青光眼、视神经脊髓炎、视神经炎和神经纤维瘤病;然而,视神经损伤和死亡的分子机制尚不完全清楚。在这里,我们提出了高空间分辨率MALDI成像质谱(IMS)分析的脂质和蛋白质,以确定人类视神经的分子解剖。在对应于有髓和无髓神经区域以及支持结缔组织、神经胶质细胞和血管的离散解剖区域中观察到许多脂质的定位。波形蛋白(一种已知的星形胶质细胞的中间丝标记物)的蛋白质片段在筛板区域的神经纤维束周围观察到。S100 B也被发现在支持神经胶质细胞区的前板层区域,和血红蛋白α亚基观察到血管区。MALDI IMS定义的视神经的分子解剖学为研究致盲人类疾病的生化变化提供了坚实的基础。
The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.