title: Lgr5⁺ amacrine cells possess regenerative potential in the retina of adult mice.
abstract: Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5(+) amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5(+) amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5(+) amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Mengfei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Shenghe
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Glasgow
authors.affiliation: Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Gibson
authors.affiliation: Department of Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Christen E
authors.initials: CE
authors.lastname: Shiber
authors.affiliation: Department of Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.|UPMC Eye Center, Eye and Ear Institute, Pittsburgh, PA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Funderburgh
authors.affiliation: Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Watkins
authors.affiliation: Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jon W
authors.initials: JW
authors.lastname: Johnson
authors.affiliation: Department of Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.|UPMC Eye Center, Eye and Ear Institute, Pittsburgh, PA, USA.|Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.|UPMC Eye Center, Eye and Ear Institute, Pittsburgh, PA, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Liu
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D063928:Ependymoglial Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D055879:Gene Knock-In Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*
chemical_list: C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Lgr5; aging; amacrine cells; neurogenesis; retina; retinal regeneration