视网膜再生中调控Müller细胞重编程的表观遗传修饰和微环境因素研究进展  

Research progress in epigenetic and microenvironment factors affecting Müller glia reprogramming in retinal regeneration

作　　者：廖怿 何婉玲 LIAO Yi;HE Wanling(Xiamen University Affiliated Xiamen Eye Center,Eye Institute of Xiamen University,School of Medicine,Xiamen University,Xiamen 361102,China;Fujian Provincial Key Laboratory of Ophthalmology and Visual Science,Fujian Engineering and Research Center of Eye Regenerative Medicine,Xiamen 361102,China)

机构地区：[1]厦门大学医学院,厦门大学附属厦门眼科中心,厦门大学眼科研究所,福建厦门361102 [2]福建省眼科与视觉科学重点实验室,福建省眼再生医学工程研究中心,福建厦门361102

出　　处：《厦门大学学报（自然科学版）》2024年第5期850-866,共17页Journal of Xiamen University：Natural Science

基　　金：厦门市自然科学基金(3502Z202373024)。

摘　　要：[背景]Müller细胞(Müller glia,MG)重编程是视网膜再生领域的研究热点.与斑马鱼(Danio rerio)不同,哺乳动物视网膜损伤后MG丧失再生视网膜能力,发生反应性胶质化产生胶质瘢痕,导致哺乳动物MG重编程再生视网膜能力丧失的分子机制仍存在许多不清楚之处.[进展]随着干细胞理论和研究方法的不断进步,越来越多研究利用单细胞测序等技术从转录、表观遗传修饰、细胞外微环境等多层次深入挖掘视网膜再生中MG重编程的调控机制,以期实现哺乳动物的视网膜再生.本文总结了不同物种中已发现的影响MG重编程能力差异的关键分子,着重关注表观遗传修饰和微环境因素.[展望]视网膜再生中MG重编程是受细胞内外多种因素协同调控的复杂过程.对斑马鱼和哺乳动物视网膜再生中MG重编程影响因素进行详细的对比分析,将有助于突破哺乳动物视网膜再生瓶颈,为开发有临床转化潜力的疗法提供新的途径.[Background]Multiple retinal diseases,including diabetic retinopathy,age-related macular degeneration,retinitis pigmentosa,and glaucoma,cause irreversible vision loss in patients and currently lack effective therapies.In recent years,with the development of both theories and technologies,novel therapies based on exogenous stem cells transplantation or endogenous stem cells have raised hope for people who are blind.Although endogenous stem cells have not be identified in the adult retina,Müller glia(MG)have been found to possess the ability/potential to regenerate retinal neurons.Specifically,zebrafish(Danio rerio)MG could follow three steps,including proliferate,reprogram into progenitor cells,and differentiate into retinal neurons,to regenerate lost neurons after injury.However,mammalian MG only transiently express the cell cycle and progenitor cell markers after injury,quickly exiting the cell cycle to enter reactive gliosis,ultimately forming retinal scars.Based on these findings,a critical approach to curing blinding retinal diseases is to reignite the regeneration capabilities of mammalian MG.[Progress]Through in-depth analysis of the regeneration molecular program of zebrafish MG and detailed comparisons between zebrafish and mammalian MG,multiple transcription factors have been identified to affect the regenerative abilities of MG.Accordingly,scientists have been able to use a combination of transcription factors to reprogram mammalian MG into retinal neuron-like cells in vitro and in vivo.In addition to transcription factors,cell fate could be affected by epigenetic and microenvironment factors.Thus,in this paper we review recent research progress in these two areas.At the epigenetic level,although the reduction of DNA methylation could facilitate the reprogramming of MG at the early stage,the proliferation and migration of MG derived progenitor cells(MGPCs)might require de novo DNA methylation at the promoter regions of some critical genes.Additionally,histone acetylation is important for the formation

关 键 词：MÜLLER细胞 视网膜再生 表观遗传修饰 微环境 

分 类 号：R774.1[医药卫生—眼科]