Organoid-derived human retinal progenitor cells promote early dedifferentiation of Müller glia in Royal College of Surgeons rats  

作　　者：Qiang Guo Yu-Xiao Zeng Shu-Dong Huang Ting Zou Zheng-Qin Yin 

机构地区：[1]Southwest Hospital/Southwest Eye Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China [2]Key Lab of Visual Damage and Regeneration&Restoration of Chongqing,Chongqing 400038,China

出　　处：《International Journal of Ophthalmology(English edition)》2023年第4期483-498,共16页国际眼科杂志（英文版）

基　　金：Supported by the National Key Research and Development Program of China(No.2018YFA0107302);the Natural Science Foundation of Chongqing,China(No.cstc2021jcyj-msxm X0437)。

摘　　要：AIM:To explore whether the subretinal transplantation of retinal progenitor cells from human embryonic stem cell-derived retinal organoid(h ERO-RPCs)could promote Müller glia dedifferentiation and transdifferentiation,thus improving visual function and delaying retinal degenerative progression.METHODS:h ERO-RPCs were subretinally transplanted into Royal College of Surgeons(RCS)rats.Electroretinography(ERG)recording was performed at 4 and 8wk postoperation to assess retinal function.Using immunofluorescence,the changes in outer nuclear layer(ONL)thickness and retinal Müller glia were explored at 2,4,and 8wk postoperation.To verify the effect of h ERO-RPCs on Müller glia in vitro,we cocultured h ERO-RPCs with Müller glia with a Transwell system.After coculture,Ki67 staining and quantitative polymerase chain reaction(q PCR)were performed to measure the proliferation and m RNA levels of Müller glia respectively.Cell migration experiment was used to detect the effect of h ERO-RPCs on Müller glial migration.Comparisons between two groups were performed by the unpaired Student’s t-test,and comparisons among multiple groups were made with one-way ANOVA followed by Tukey’s multiple comparison test.RESULTS:The visual function and ONL thickness of RCS rats were significantly improved by transplantation of h ERO-RPCs at 4 and 8wk postoperation.In addition to inhibiting gliosis at 4 and 8wk postoperation,h ERO-RPCs significantly increased the expression of dedifferentiation-associated transcriptional factor in Müller glia and promoted the migration at 2,4 and 8wk postoperation,but not the transdifferentiation of these cells in RCS rats.In vitro,using the Transwell system,we found that h ERO-RPCs promoted the proliferation and migration of primary rat Müller glia and induced their dedifferentiation at the m RNA level.CONCLUSION:These results show that h ERO-RPCs might promote early dedifferentiation of Müller glia,which may provide novel insights into the mechanisms of stem cell therapy and Müller glial reprogram

关 键 词：retinal degeneration retinal organoid retinal progenitor cells subretinal transplantation Muller glia DEDIFFERENTIATION 

分 类 号：R774.1[医药卫生—眼科]