The Influence of Mitochondrial Dynamics and Function on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease.
The Influence of Mitochondrial Dynamics and Function on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease.
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线粒体动力学和功能对视神经疾病视网膜神经节细胞易感性的影响
DOI：
10.3390/cells10071593
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发表时间：
2021-06-25
期刊：
影响因子：
6
通讯作者：
Nickells RW
中科院分区：
文献类型：
--
作者：
Muench NA;Patel S;Maes ME;Donahue RJ;Ikeda A;Nickells RW
线粒体功能和功能障碍在神经退行性变过程中的重要作用已被广泛认识。就线粒体功能障碍而言，视网膜神经节细胞(RGC)似乎是中枢神经系统中一种高度脆弱的神经细胞类型，但其实际原因仍不完全清楚。这些细胞有一个独特的环境，无髓轴突必须弯曲近90°才能离开眼睛，然后穿过跨层压力梯度，才能在视神经中形成有髓鞘。这一区域，即视神经头，包含了这些细胞中密度最高的线粒体。青光眼是发生在这个部位的一系列事件的完美风暴，跨层压力梯度的变化和支持神经胶质细胞的代谢支持功能的重新分配相结合，似乎对RGC轴突施加了更多的代谢应激，导致轴突运输机制失效。然而，RGC本身也对基因突变非常敏感，特别是在影响线粒体动力学和线粒体清除的基因上。这些突变会系统性地影响每个细胞中的线粒体，通常会导致视神经病变，作为受影响患者的唯一病理缺陷。本文综述了有关线粒体结构和功能的知识，以及已知的神经元能量需求，并将这些放在视网膜节细胞线粒体的正常和病理特征的背景下。
The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs.
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影响因子：
3.7
作者：
Cartoni R;Pekkurnaz G;Wang C;Schwarz TL;He Z
通讯作者：
He Z
影响因子：
4.2
作者：
Balaratnasingam, Chandrakumar;Pham, Duy;Yu, Dao-Yi
通讯作者：
Yu, Dao-Yi
影响因子：
3
作者：
Aiello, GL;Bach-y-Rita, P
通讯作者：
Bach-y-Rita, P
影响因子：
5.3
作者：
Bergaglio T;Luchicchi A;Schenk GJ
通讯作者：
Schenk GJ
影响因子：
4.2
作者：
Alward, WLM;Kwon, YH;Stone, EM
通讯作者：
Stone, EM