title: Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells.
abstract: Rare retinal stem cells (RSCs) within the ciliary epithelium at the retinal margin of the adult mouse and human eyes can divide in vitro in the absence of growth factors to generate clonal, self-renewing spheres which can generate all the retinal cell types. Since no regenerative properties are seen in situ in the adult mammalian eye, we sought to determine the factors that are involved in the repression of endogenous RSCs. We discovered that factors secreted by the adult lens and cornea block the proliferation of adult RSCs in vitro. Bone morphogenetic protein (BMP)2, BMP4, and secreted frizzled related protein 2 were identified as principal effectors of the anti-proliferative effects on RSCs. As a similar induced quiescence was observed in vitro on both mouse and human RSCs, targeting these molecules in vivo may reactivate RSCs directly in situ in the eyes of the blind.
authors.affiliation: Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research University of Toronto, Toronto, Ontario, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Balenci
authors.forename: Carl
authors.initials: C
authors.lastname: Wonders
authors.forename: Brenda L K
authors.initials: BL
authors.lastname: Coles
authors.forename: Laura
authors.initials: L
authors.lastname: Clarke
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003315:Cornea / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000166:cytology; D018874:Spheroids, Cellular / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D046509:Tissue Culture Techniques; D000099176:Noggin Protein; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D008565:Membrane Proteins; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins
keywords: Adult retinal stem cells; Bone morphogenetic proteins; Cornea; Lens; Quiescence; Secreted Frizzled Related Protein 2