Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
Prog Retin Eye Res. 2013 Sep;36:217-46. doi: 10.1016/j.preteyeres.2013.07.001. Epub 2013 Jul 23.
Retinal ganglion cells (RGCs) are specialized projection neurons that relay an immense amount of visual information from the retina to the brain. RGC signal inputs are collected by dendrites and output is distributed from the cell body via very thin (0.5-1 μm) and long (∼50 mm) axons. The RGC cell body is larger than other retinal neurons, but is still only a very small fraction (one ten thousandths) of the length and total surface area of the axon. The total distance traversed by RGCs extends from the retina, starting from synapses with bipolar and amacrine cells, to the brain, to synapses with neurons in the lateral geniculate nucleus. This review will focus on the energy demands of RGCs and the relevant tissues that surround them. RGC survival and function unexceptionally depends upon free energy, predominantly adenosine triphosphate (ATP). RGC energy metabolism is vastly different when compared to that of the photoreceptors. Each subcellular component of the RGC is remarkably different in terms of structure, function and extracellular environment. The energy demands and distribution of each component are also distinct as evidenced by the uneven distribution of mitochondria and ATP within the RGC - signifying the presence of intracellular energy gradients. In this review we will describe RGCs as having four subcellular components, (1) Dendrites, (2) Cell body, (3) Non-myelinated axon, including intraocular and optic nerve head portions, and (4) Myelinated axon, including the intra-orbital and intracranial portions. We will also describe how RGCs integrate information from each subcellular component in order achieve intracellular homeostatic stability as well as respond to perturbations in the extracellular environment. The possible cellular mechanisms such as axonal transport and axonal cytoskeleton proteins that are involved in maintaining RGC energy homeostasis during normal and disease conditions will also be discussed in depth. The emphasis of this review will be on energetic mechanisms within RGC components that have the most relevance to clinical ophthalmology.
视网膜神经节细胞(RGCs)是专门的投射神经元,它们将大量来自视网膜的视觉信息传递到大脑。RGC 的信号输入由树突收集,输出则通过非常细(0.5-1μm)且长(约 50mm)的轴突从细胞体分布。RGC 细胞体比其他视网膜神经元大,但仍只占轴突长度和总表面积的很小一部分(万分之一)。RGC 穿越的总距离从视网膜开始,从与双极细胞和无长突细胞的突触延伸到大脑,再到与外侧膝状体核神经元的突触。本综述将重点关注 RGC 及其周围相关组织的能量需求。RGC 的存活和功能无一例外地依赖于自由能,主要是三磷酸腺苷(ATP)。与光感受器相比,RGC 的能量代谢有很大的不同。RGC 的每个亚细胞成分在结构、功能和细胞外环境方面都有显著的不同。由于 RGC 内线粒体和 ATP 的不均匀分布——这表明存在细胞内能量梯度,因此每个成分的能量需求和分布也不同。在本综述中,我们将 RGC 描述为具有四个亚细胞成分,(1)树突,(2)细胞体,(3)无髓鞘轴突,包括眼内段和视神经头部,以及(4)有髓鞘轴突,包括眶内段和颅内段。我们还将描述 RGC 如何整合来自每个亚细胞成分的信息,以实现细胞内的稳态稳定性,并对外界环境的变化做出反应。在正常和疾病条件下,涉及维持 RGC 能量稳态的可能的细胞机制,如轴突运输和轴突细胞骨架蛋白,也将在本文中进行深入讨论。本综述的重点将放在与临床眼科最相关的 RGC 成分的能量机制上。