Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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外文摘要：Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex class Ⅱ molecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

外文关键词：

cell therapyimmune recognitionmajor histocompatibility complex class Ⅱ(MHCII)neuroprotectionolfactory ensheathing gliaretinal ganglion cells

作者：

María Norte-Muñoz、María Portela-Lomba、Paloma Sobrado-Calvo、Diana Simón、Johnny Di Pierdomenico、Alejandro Gallego-Ortega、Mar Pérez、José M.Cabrera-Maqueda、Javier Sierra、Manuel Vidal-Sanz、María Teresa Moreno-Flores、Marta Agudo-Barriuso

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作者单位：

Grupo de Investigación Oftalmología Experimental,Departamento de Oftalmología,Optometría,Otorrinolaringología y Anatomía Patológica,Facultad de Medicina,Universidad de Murcia,Instituto Murciano de Investigación Biosanitaria(IMIB),Campus de Ciencias de la Salud,Murcia,Spain

Experimental Sciences Faculty,Universidad Francisco de Vitoria,Pozuelo de Alarcón,Madrid,Spain

Department of Genetics and Development,Columbia University Medical Center,New York,NY,USA

Anatomy,Histology and Neuroscience Department,Medicine Faculty,Universidad Autónoma de Madrid,Madrid,Spain

Center of Neuroimmunology,Service of Neurology,Laboratory of Advanced Imaging in Neuroimmunological Diseases,Hospital Clinic of Barcelona,Institut d'Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS),and Universitat de Barcelona,Barce

Medicine Faculty,Universidad Francisco de Vitoria,Pozuelo de Alarcón,Madrid,Spain

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01631

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(8)