综述
ENGLISH ABSTRACT
外伤性视神经损伤及间充质干细胞治疗作用研究进展
袁湘玲
姚瑶
伍子建 [综述]
作者及单位信息
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DOI: 10.3760/cma.j.cn115989-20210717-00416
Mesenchymal stem cell therapies for traumatic optic nerve injury
Yuan Xiangling
Yao Yao
Ng Tsz Kin
Authors Info & Affiliations
Yuan Xiangling
Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou 515041, China
Yao Yao
Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou 515041, China
Ng Tsz Kin
Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou 515041, China
·
DOI: 10.3760/cma.j.cn115989-20210717-00416
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摘要

外伤性视神经损伤引起的视网膜神经节细胞(RGC)继发性死亡和轴突丢失是导致不可逆性视功能损害的主要原因。视神经受损后RGC的快速死亡及复杂的死亡途径致使临床治疗效果收效甚微。近年来,干细胞的潜能成为神经退行性病变组织修复再生的新治疗手段。成体干细胞,尤其是间充质干细胞(MSC),因其免疫调控特性和神经保护作用,在外伤性视神经损伤修复治疗上被广泛研究。MSC以旁分泌神经营养因子、释放外泌体及细胞移植直接接触受损组织等方式发挥神经保护作用促进RGC存活及轴突再生,并经处理后可增强其干细胞特性;此外,MSC可被诱导转分化为RGC,发挥细胞替代治疗的修复作用。本文将总结MSC在外伤性视神经损伤治疗方面的动物实验和临床研究进展,以及其作用机制,同时归纳了增强MSC神经保护作用的方法,还探讨未来MSC在外伤性视神经损伤上的发展方向,这有利于今后制定更完善可靠的MSC应用于外伤性视神经损伤的治疗策略。

外伤性视神经损伤;间充质干细胞;视网膜神经节细胞;神经保护作用;细胞替代治疗
ABSTRACT

Optic nerve injury by trauma would lead to secondary retinal ganglion cell (RGC) death and axonal loss, which are the causes of irreversible visual impairment and even blindness.Currently, there is still no effective clinical treatment to cure optic nerve injury owing to limited regeneration or recovery and complex death mechanism in RGCs.Recently, stem cell therapy has been proposed as a viable treatment strategy for optic nerve injury.Adult stem cells, especially mesenchymal stem cells (MSCs) have been widely studied in animal models and tested in clinical trials for optic neuropathies.MSCs could promote RGC survival and axonal regeneration by their neuroprotective effects, including neurotrophic factor and exosome secretion, cell-cell contact and immunomodulation.The neuroprotective properties of MSCs could further be enhanced by preconditioning.In addition, MSCs are also able to be induced and transdifferentiate into RGC for potential cell replacement therapy.This article reviews the applications of MSCs in optic nerve injury treatment and their related mechanisms, summarizes the strategies to enhance the neuroprotective effects of human MSCs and discusses the future prospects of MSCs for optic nerve injury treatment to present the diversified function of MSCs, which will help formulate a more complete and reliable treatment strategy for MSC application in traumatic optic nerve injury in the future.

Traumatic optic neuropathy;Mesenchymal stem cells;Retinal ganglion cells;Neuroprotection;Cell replacement therapy
Ng Tsz Kin, Email: grodef.cabeisjjzw

Yuan Xiangling and Yao Yao contributed equally to this article

引用本文

袁湘玲,姚瑶,伍子建. 外伤性视神经损伤及间充质干细胞治疗作用研究进展[J]. 中华实验眼科杂志,2025,43(01):69-79.

DOI:10.3760/cma.j.cn115989-20210717-00416

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外伤性视神经损伤是一种对视神经产生直接或间接性损伤继而引起视网膜神经节细胞(retinal ganglion cell,RGC)继发性死亡和轴突丢失的疾病,根据病因可将其分为直接性外伤性视神经损伤和间接性外伤性视神经损伤。直接性外伤性视神经损伤主要是由于穿透性损伤造成的撕裂伤,以及因骨折或眼眶出血所造成的锐伤或顿挫伤。间接性外伤性视神经损伤大多是因为脑部受到撞击,冲击力通过颅骨传递至视神经和视网膜,导致眼压升高并损伤RGC。视神经一旦受损将造成视力下降、视野缺损、色觉减退及视神经萎缩,最后导致不可逆性的视力受损或致盲,严重影响患者的生活质量 [ 1 ]。据统计,在闭合性头部创伤患者中有0.5%~5%伴有视神经损伤,且受累人群主要为青壮年 [ 2 ]
目前临床上用于治疗外伤性视神经损伤的方法有限,主要有保守观察、激素疗法和手术治疗 [ 2 ]。尽管这些方法可一定程度上延缓视神经损伤的进程,但大部分患者的RGC数量仍在不断减少,视功能改善程度有限,治疗效果不佳,目前尚无一种临床治疗方式能有效修复受损的RGC及其轴突。近年来,大量研究探索有效的视神经损伤疾病的治疗方法,并在动物实验中有很大的进展 [ 3 ];但能在临床上进行应用的且能促进修复受损RGC的治疗措施依旧有限。因此,深入了解外伤性视神经损伤中RGC死亡机制有助于发现新药物靶点及制定治疗方案。
随着干细胞和再生医学技术的快速发展,将干细胞应用于外伤性视神经损伤修复治疗的研究日益增多。大部分研究仍处于动物实验阶段,但也有研究团队已开展干细胞治疗视神经疾病的临床试验。本文将集中梳理、归纳和总结间充质干细胞治疗修复外伤性视神经损伤的研究,并对目前应用干细胞修复外伤性视神经损伤存在的问题和未来可能发展方向进行探讨。
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伍子建,Email: grodef.cabeisjjzw
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袁湘玲与姚瑶对本文有同等贡献

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所有作者均声明不存在利益冲突
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广东省基础与应用基础研究基金区域联合基金—青年基金 (2019A1515110685)
广东省中医药建设专项资金面上项目 (20202089)
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