综述
ENGLISH ABSTRACT
人角膜基质细胞的表型研究进展
杨怡
牛阳 [综述]
袁玲 [综述]
作者及单位信息
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DOI: 10.3760/cma.j.cn115989-20200626-00455
Progress on the phenotype of human corneal stromal cells
Yang Yi
Niu Yang
Yuan Ling
Authors Info & Affiliations
Yang Yi
School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, China
Niu Yang
Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, China
Yuan Ling
School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China
·
DOI: 10.3760/cma.j.cn115989-20200626-00455
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摘要

人角膜基质细胞(HCSCs)是一类呈静息状态的神经嵴间充质细胞,是负责分泌基质的高度特化的透明组织,在维持角膜透明度和人眼正常视觉功能等方面发挥重要作用。正常情况下,角膜基质细胞呈静息状态并表现为扁平、树突状,在角膜受到创伤刺激后被激活,激活状态的人角膜基质细胞(HCK)向修复表型转变,发生凋亡或向角膜成纤维细胞表型和肌成纤维细胞表型转化。HCSCs的表型转化与人角膜损伤修复过程所引起的瘢痕组织形成以及角膜透明度降低等方面具有密切关系。本文通过对HCSCs的3种表型、表型标志物、表型间转化以及体外转化的机制进行综述,发现通过干预HCK向纤维化表型转化过程及TGF-β/Smad等相关信号通路可以抑制角膜纤维化。因此,深入研究HCSCs表型转化的分子机制及干预角膜瘢痕形成的调控机制,有助于临床防治患者角膜纤维化和角膜术后混浊。

人角膜基质细胞;细胞表型;体外转化
ABSTRACT

Human corneal stromal cells (HCSCs), a type of resting neural crest mesenchymal cell, are highly specialized transparent tissues responsible for the secretion of stroma and play an important role in maintaining the transparency of the cornea and the normal visual function of human eye.Normally, corneal stromal cells are quiescent, flat and dendritic.After the cornea is stimulated by trauma, the corneal stromal cells will be activated, and the activated human corneal keratocytes (HCK) will turn to a repair phenotype, undergo apoptosis or transform to corneal fibroblast phenotype and myofibroblast phenotype.The phenotype transformation of HCSCs is closely related to the formation of scar tissue and the reduction of ocular transparency caused by the repair process of human corneal injury.In this article, three phenotypes, phenotypic markers, phenotype transformation and in vitro transformation mechanisms of HCSCs were reviewed, and it was found that corneal fibrosis could be inhibited by interfering with the transformation process of HCK to fibrotic phenotype and TGF-β/Smad signaling pathways.Therefore, in-depth study of the molecular mechanism of phenotypic transformation of HCSCs and the regulatory mechanism of intervention in corneal scarring formation is helpful for prevention and treatment of corneal fibrosis and postoperative corneal opacity in patients.

Human corneal stromal cells;Cell phenotype;Transformation in vitro
Yuan Ling, Email: mocdef.qabqxdkyxn
引用本文

杨怡,牛阳,袁玲. 人角膜基质细胞的表型研究进展[J]. 中华实验眼科杂志,2022,40(09):874-879.

DOI:10.3760/cma.j.cn115989-20200626-00455

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人角膜基质细胞(human corneal stromal cells,HCSCs)是正常角膜基质层中的主要细胞成分,存在于平行排列的胶原纤维之间,通过细胞突起顶部的间隙进行相邻细胞间物质信息传递 [ 1 ];其具有合成和分泌细胞外基质(extracellular matrix,ECM)成分,如胶原蛋白、糖胺聚糖、基质金属蛋白酶(matrix metalloproteinase,MMP)以及受到刺激后向角膜细胞修复表型转化的功能,在维持角膜结构完整性和创伤修复中发挥重要作用 [ 2 ]
人角膜基质创伤愈合是一个非常复杂的过程,当角膜基质层受到创伤、感染或手术后,处于静息状态的HCSCs被刺激,转变为激活状态的人角膜基质细胞(human corneal keratocytes,HCK),继而发生死亡或转化为修复表型,引起角膜基质混浊,角膜深层出现新生血管、持续性炎症反应、纤维化甚至是不同程度的角膜瘢痕,导致畏光和视力下降等临床症状 [ 3 ]。感染性角膜溃疡、免疫紊乱(如圆锥角膜等)以及目前临床应用激光矫正视力角膜手术(如准分子激光手术、激光光学角膜切削术等)均能引起角膜基质混浊和瘢痕 [ 4 ]。同时HCSCs的结构和功能发生变化可导致角膜的透明度降低,使视力受到损害。因此,深入研究HCSCs表型的转化过程以及其调控机制,不仅有助于了解角膜损伤修复的发展过程,而且对于发现、预防和治疗角膜基质纤维化、减少瘢痕形成,甚至逆转瘢痕损伤程度,具有重要的临床意义。本文就HCSCs表型、标志物、表型的转化及其体外转化机制进行综述,以期为发现新的临床治疗手段提供思路。
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备注信息
A
袁玲,Email: mocdef.qabqxdkyxn
B
本文得到了美国哈佛大学医学院Schepens研究所Zieske实验室和Ciolino实验室的共同指导和帮助
C
所有作者均声明不存在利益冲突
D
国家自然科学基金项目 (81960836)
国家留学基金委西部地区人才培养特别项目 (201908645028)
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