Müller cell metabolic chaos during retinal degeneration.
Müller cell metabolic chaos during retinal degeneration.
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DOI：
10.1016/j.exer.2016.04.022
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发表时间：
2016-09
影响因子：
3.4
通讯作者：
Jones, Bryan W.
中科院分区：
文献类型：
--
作者：
Pfeiffer, Rebecca L.;Marc, Robert E.;Kondo, Mineo;Terasaki, Hiroko;Jones, Bryan W.
关键词：
Müller细胞在视网膜代谢中起着关键作用，并且是最早证明视网膜应激或疾病中代谢变化的细胞之一。这些变化的时间、程度、监管和影响尚不清楚。我们评估了Müller细胞在变性视网膜中的代谢表型。从野生型（WT）和视紫红质Tg P347 L兔收获的视网膜固定在混合醛和树脂包埋的计算分子表型（CMP）。CMP促进视网膜中每个细胞的小分子指纹识别，允许评估单细胞中的代谢物水平。CMP揭示了来自TgP347L视网膜的Müller细胞中代谢物水平的特征变化。简而言之，邻近的Müller细胞表现出牛磺酸、谷氨酸、谷氨酰胺、谷胱甘肽、谷氨酰胺合成酶（GS）和CRALBP的变异性。这种变异性表明代谢产物之间没有相关性，这意味着这些变化在功能上是混乱的，而不是简单的异质性。任何聚类算法都不能将Müller细胞分类为TgP347 L视网膜中的单一类别，这是目前退化视网膜中代谢变异性的正式证据。虽然视网膜变性肯定是触发因素，但Müller细胞代谢改变并不是对微环境的一致反应。虽然GS被认为是负责视网膜中谷氨酸盐转化为谷氨酰胺的主要酶，但在退化的视网膜中，替代途径似乎未被掩盖。不知何故，长期重塑涉及Müller细胞协调和身份的丧失，这对仅针对神经元的治疗干预具有负面影响。
Müller cells play a critical role in retinal metabolism and are among the first cells to demonstrate metabolic changes in retinal stress or disease. The timing, extent, regulation, and impacts of these changes are not yet known. We evaluated metabolic phenotypes of Müller cells in the degenerating retina. Retinas harvested from wild-type (WT) and rhodopsin Tg P347L rabbits were fixed in mixed aldehydes and resin embedded for computational molecular phenotyping (CMP). CMP facilitates small molecule fingerprinting of every cell in the retina, allowing evaluation of metabolite levels in single cells. CMP revealed signature variations in metabolite levels across Müller cells from TgP347L retina. In brief, neighboring Müller cells demonstrated variability in taurine, glutamate, glutamine, glutathione, glutamine synthetase (GS), and CRALBP. This variability showed no correlation across metabolites, implying the changes are functionally chaotic rather than simply heterogeneous. The inability of any clustering algorithm to classify Müller cell as a single class in the TgP347L retina is a formal proof of metabolic variability in the present in degenerating retina. Although retinal degeneration is certainly the trigger, Müller cell metabolic alterations are not a coherent response to the microenvironment. And while GS is believed to be the primary enzyme responsible for the conversion of glutamate to glutamine in the retina, alternative pathways appear to be unmasked in degenerating retina. Somehow, long term remodeling involves loss of Müller cell coordination and identity, which has negative implications for therapeutic interventions that target neurons alone.
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影响因子：
2.5
作者：
Jones, Bryan William;Kondo, Mineo;Terasaki, Hiroko;Watt, Carl Brock;Rapp, Kevin;Anderson, James;Lin, Yanhua;Shaw, Marguerite Victoria;Yang, Jia-Hui;Marc, Robert Edward
通讯作者：
Marc, Robert Edward
影响因子：
2.4
作者：
Jones, B. W.;Kondo, M.;Terasaki, H.;Lin, Y.;McCall, M.;Marc, R. E.
通讯作者：
Marc, R. E.
影响因子：
5.2
作者：
Bringmann, Andreas;Grosche, Antje;Reichenbach, Andreas
通讯作者：
Reichenbach, Andreas
影响因子：
1.8
作者：
Chader, GJ
通讯作者：
Chader, GJ
DOI：
10.1073/pnas.92.23.10545
发表时间：
1995-11-07
影响因子：
11.1
作者：
BROCKERHOFF, SE;HURLEY, JB;DOWLING, JE
通讯作者：
DOWLING, JE