中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (8): 1198-1200.doi: 10.4103/1673-5374.162691

• 观点:视神经损伤修复保护与再生 • 上一篇    下一篇

轴突细胞骨架蛋白在人视神经乳头中:一种治疗青光眼及其他视神经病变的新方法

  

  • 收稿日期:2015-05-27 出版日期:2015-08-24 发布日期:2015-08-24

Distribution pattern of axonal cytoskeleton proteins in the human optic nerve head

Min Hye Kang, Dao-Yi Yu   

  1. Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, WA, Australia; Lions Eye Institute, 2 Verdun Street, Nedlands, WA, Australia
  • Received:2015-05-27 Online:2015-08-24 Published:2015-08-24
  • Contact: Dao-Yi Yu, Ph.D., dyyu@lei.org.au.

摘要:

青光眼是一种进行性视神经病变,伴随视网膜神经节细胞轴突的结构以及视功能缺损。青光眼可通过视网膜神经节细胞轴突选择性丧失从其他视神经病变中区分。上,下周围神经区域是最容易受到压力引起损伤的部位,而内颞区域则适应能力最强。但我们对轴索损伤模式背后的发病机制仍知之甚少。人类视网膜神经节细胞的结构是复杂的,包含在内视网膜细胞体中,通过一个超过50毫米长的轴突连接到其目标突触,它的平均轴突直径只有0.72微米。因为视网膜神经节细胞轴突在通过若干不同机制和细胞外环境时会沿着其预定路径经过一个很长距离,因此可以推测细胞骨架在维持轴突完整性方面将发挥关键作用。细胞骨架蛋白在视神经头的分布可会为每个隔室内的轴突损伤提供有关能量学和脆弱性的有价值信息。轴突细胞骨架蛋白本身与视网膜神经节细胞的健康和疾病相关。中间丝,微管,肌动蛋白丝和微管相关蛋白构成了轴突细胞骨架。此外,区域骨架蛋白浓度的结构决定因素包括髓鞘蛋白和线粒体分布图案。线粒体细胞器,髓鞘蛋白含量和神经组织压力的变化以及人类视网膜神经节细胞轴突的长度可能会影响细胞骨架蛋白亚基的集中区域。这可能有助于解释为什么许多疾病的视神经乳头部都以非对称的方式受损,包括青光眼。

Abstract:

Distribution pattern of axonal cytoskeleton proteins in the human optic nerve head拒Glaucoma is one of the leading causes of blindness in developed world. It is progressive optic neuropathy where structural loss of retinal ganglion cell (RGC) axons corresponds with functional visual field defect. Glaucoma is distinguished from other optic neuropathies by its selective loss of RGC axons. Superior and inferior peripheral nerve sectors are found to be most vulnerable to pressure induced injury whereas inner temporal sector is most resilient. Pathogenesis behind the preferential axonal damage pattern is still poorly understood. Prof. Dao-Yi Yu (The University of Western Australia) showed that as RGC axons traverse a long distance through a number of different mechanical and extracellular environments along their projected path, it is expected that the cytoskeleton will play a critical role in maintaining axonal integrity. The distribution of cytoskeleton protein in the optic nerve head may therefore provide valuable information regarding the energetics and vulnerability of axonal injury in each compartment. Axonal cytoskeleton proteins are inherently linked to RGC health and disease. Intermediate filaments, microtubules, actin filament and microtubule associated proteins (MAPs) constitute axonal cytoskeletons. Cytoskeleton protein behaviour is shaped by physiological variables such as absolute tissue pressure and pressure gradients. Additionally, structural determinants of regional cytoskeleton protein concentration include myelin proteins and the pattern of mitochondrial distribution. The variation in mitochondrial organelle, myelin protein content and neural tissue pressure along the length of the human RGC axon could potentially influence the regional concentration of cytoskeleton protein subunits. This may help explain why the optic nerve head is injured in an asymmetrical fashion in many diseases including glaucoma.