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Soxllb regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish

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Neural regeneration Research 2023年第2期18卷 445-450页

作者： Kaida Song Zihao Lin Lining Cao Bowen Lu Yuxi Chen Shuqiang Zhang Jianfeng Lu Hui Xu Key Lab of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Shanghai YangZhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina

The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.

关键词： cell migration fate determination Müllerglia Müller glia-derived progenitor Notch signaling photoreceptor retina regeneration Sox11 transcription factor zebrafish

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Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

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Neural regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui Kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration

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retina stem cells,hopes and obstacles

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World Journal of Stem Cells 2021年第10期13卷 1446-1479页

作者： Olga L German Harmonie Vallese-Maurizi Tamara B Soto Nora P Rotstein Luis Enrique Politi Department of Biology Biochemistry and PharmacyUniversidad Nacional del SurBahia blanca 8000Buenos AiresArgentina Department of Biology Biochemistry and PharmacyUniversidad Nacional del Surand Neurobiology DepartmentInstituto de Investigaciones Bioquímicas de Bahía Blanca(INIBIBB)ConicetBahía Blanca 8000Buenos AiresArgentina

retinal degeneration is a major contributor to visual dysfunction worldwide.Although it comprises several eye diseases,loss of retinal pigment epithelial(RPE)and photoreceptor cells are the major contributors to their pathogenesis.Early therapies included diverse treatments,such as provision of anti-vascular endothelial growth factor and many survival and trophic factors that,in some cases,slow down the progression of the degeneration,but do not effectively prevent it.The finding of stem cells(SC)in the eye has led to the proposal of cell replacement strategies for retina degeneration.Therapies using different types of SC,such as retinal progenitor cells(RPCs),embryonic SC,pluripotent SCs(PSCs),induced PSCs(iPSCs),and mesenchymal stromal cells,capable of self-renewal and of differentiating into multiple cell types,have gained ample support.Numerous preclinical studies have assessed transplantation of SC in animal models,with encouraging results.The aim of this work is to revise the different preclinical and clinical approaches,analyzing the SC type used,their efficacy,safety,cell attachment and integration,absence of tumor formation and immunorejection,in order to establish which were the most relevant and successful.In addition,we examine the questions and concerns still open in the field.The data demonstrate the existence of two main approaches,aimed at replacing either RPE cells or photoreceptors.Emerging evidence suggests that RPCs and iPSC are the best candidates,presenting no ethical concerns and a low risk of immunorejection.Clinical trials have already supported the safety and efficacy of SC treatments.Serious concerns are pending,such as the risk of tumor formation,lack of attachment or integration of transplanted cells into host retinas,immunorejection,cell death,and also ethical.However,the amazing progress in the field in the last few years makes it possible to envisage safe and effective treatments to restore vision loss in a near future.

关键词： retina regeneration Stem cells retina stem cell transplantation Cancer stem cells Photoreceptor replacement

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An insight on established retinal injury mechanisms and prevalent retinal stem cell activation pathways in vertebrate models

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Animal Models and Experimental Medicine 2021年第3期4卷 189-203页

作者： Rinchen Doma Sherpa Subhra Prakash Hui S.N.Pradhan Centre for Neurosciences University of CalcuttaKolkataIndia

Implementing different tools and injury mechanisms in multiple animal models of retina regeneration,researchers have discovered the existence of retinal stem/pro-genitor cells.Although they appear to be distributed uniformly across the vertebrate lineage,the reparative potential of the retina is mainly restricted to lower vertebrates.Regenerative repair post-injury requires the creation of a proliferative niche,vital for proper stem cell activation,propagation,and lineage differentiation.This seems to be lacking in mammals.Hence,in this review,we first discuss the many forms of retinal injuries that have been generated using animal models.Next,we discuss how they are utilized to stimulate regeneration and mimic eye disease pathologies.The key to driving stem cell activation in mammals relies on the information we can gather from these models.Lastly,we present a brief update about the genes,growth factors,and signaling pathways that have been brought to light using these models.

关键词： animal models retina injury retina regeneration retinal stem cells zebrafish

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