Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas.
Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas.
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DOI：
10.1038/s41598-017-17402-1
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发表时间：
2017-12-11
影响因子：
4.6
通讯作者：
Schey KL
中科院分区：
文献类型：
--
作者：
Anderson DMG;Ablonczy Z;Koutalos Y;Hanneken AM;Spraggins JM;Calcutt MW;Crouch RK;Caprioli RM;Schey KL
Stargardt病是一种幼年型视网膜变性，与脂褐素及其双维A酸类成分，如N-视黄醛-N-视黄醇乙醇胺(A2E)水平升高有关。然而，Stargardt的发病机制仍然知之甚少，也没有针对性的治疗方法。利用高空间和高质量分辨率的基质辅助激光解吸电离成像质谱仪，我们测定了ABCA4−/−Stargardt模型小鼠视网膜色素上皮(RPE)特异性脂谱的变化，并与其相应的背景品系进行了比较。为了准确地确定一类高表达的脂类--双(单甘酯)磷酸(BMP)脂类的性质，并将它们与同量异构体区分开来，需要对正负离子模式下的LC-MS/MS进行广泛的分析。健康人视网膜RPE中也检测到相同的BMP脂类物质。BMP脂类与内体/溶酶体储存性疾病尼曼-皮克和神经性蜡样脂褐素沉积症有关，并被报道调节内体中的胆固醇水平。这些结果表明，与晚期内体/溶酶体功能障碍相关的脂代谢紊乱可能在Stargardt病的发病机制中发挥作用，并在人类视网膜中得到证实。
Stargardt disease is a juvenile onset retinal degeneration, associated with elevated levels of lipofuscin and its bis-retinoid components, such as N-retinylidene-N-retinylethanolamine (A2E). However, the pathogenesis of Stargardt is still poorly understood and targeted treatments are not available. Utilizing high spatial and high mass resolution matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS), we determined alterations of lipid profiles specifically localized to the retinal pigment epithelium (RPE) in Abca4 −/− Stargardt model mice compared to their relevant background strain. Extensive analysis by LC-MS/MS in both positive and negative ion mode was required to accurately confirm the identity of one highly expressed lipid class, bis(monoacylgylercoro)phosphate (BMP) lipids, and to distinguish them from isobaric species. The same BMP lipids were also detected in the RPE of healthy human retina. BMP lipids have been previously associated with the endosomal/lysosomal storage diseases Niemann-Pick and neuronal ceroid lipofuscinosis and have been reported to regulate cholesterol levels in endosomes. These results suggest that perturbations in lipid metabolism associated with late endosomal/lysosomal dysfunction may play a role in the pathogenesis of Stargardt disease and is evidenced in human retinas.
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影响因子：
4.4
作者：
Grey AC;Schey KL
通讯作者：
Schey KL
通过质谱法对组织中脂质生物化学的MALDI成像。
影响因子：
62.1
作者：
Berry, Karin A. Zemski;Hankin, Joseph A.;Barkley, Robert M.;Spraggins, Jeffrey M.;Caprioli, Richard M.;Murphy, Robert C.
通讯作者：
Murphy, Robert C.
DOI：
10.1007/s13361-015-1143-9
发表时间：
2015-06-01
影响因子：
3.2
作者：
Anderson, David M. G.;Spraggins, Jeffrey M.;Schey, Kevin L.
通讯作者：
Schey, Kevin L.
影响因子：
4.3
作者：
Garrett, Timothy J.;Menger, Robert F.;Yost, Richard A.
通讯作者：
Yost, Richard A.
DOI：
10.1039/c5pp00156k
发表时间：
2015-11
期刊：
Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology
影响因子：
--
作者：
Adler L 4th;Boyer NP;Anderson DM;Spraggins JM;Schey KL;Hanneken A;Ablonczy Z;Crouch RK;Koutalos Y
通讯作者：
Koutalos Y