title: Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas.
abstract: Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats.
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.|Key Laboratory of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, 400038, China.
authors.forename: Zui
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.|Key Laboratory of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, 400038, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.|Key Laboratory of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, 400038, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jian
authors.affiliation: Save Sight Institute, South Block, Sydney Eye Hospital, Sydney, NSW, 2001, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Gillies
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.|Key Laboratory of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, 400038, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.|Key Laboratory of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, 400038, China.
authors.forename: Zheng Qin
authors.initials: ZQ
authors.lastname: Yin
mesh_terms: D000818:Animals; D002453:Cell Cycle; D054337:Cell Dedifferentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D015536:Down-Regulation; D004596:Electroretinography; D063928:Ependymoglial Cells / Q000166:cytology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000166:cytology*; D012162:Retinal Degeneration / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
chemical_list: C578027:Lin28A protein, rat; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D049452:Green Fluorescent Proteins
keywords: Lin28B; Müller glia cell; de-differentiation; let-7