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  

作　　者：María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso 

机构地区：[1]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 [2]Experimental Sciences Faculty,Universidad Francisco de Vitoria,Pozuelo de Alarcón,Madrid,Spain [3]Anatomy,Histology and Neuroscience Department,Medicine Faculty,Universidad Autónoma de Madrid,Madrid,Spain [4]Center of Neuroimmunology,Service of Neurology,Laboratory of Advanced Imaging in Neuroimmunological Diseases,Hospital Clínic of Barcelona,Institut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS),and Universitat de Barcelona,Barcelona,Spain [5]Medicine Faculty,Universidad Francisco de Vitoria,Pozuelo de Alarcón,Madrid,Spain

出　　处：《Neural Regeneration Research》2025年第8期2395-2407,共13页中国神经再生研究（英文版）

基　　金：supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS);the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB);Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de Madrid;Fundación Universidad Francisco de Vitoria(to JS)。

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 classⅡmolecules.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.

关 键 词：cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells 

分 类 号：R338[医药卫生—人体生理学]