title: Generation of retinal ganglion cells with functional axons from human induced pluripotent stem cells.
abstract: We generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells. After development of the optic vesicle from the induced stem cell embryoid body in three-dimensional culture, conversion to two-dimensional culture, achieved by supplementation with BDNF, resulted in differentiation of RGCs at a rate of nearly 90% as indicated by a marginal subregion of an extruded clump of cells, suggesting the formation of an optic vesicle. Axons extended radially from the margin of the clump. Induced RGCs expressed specific markers, such as Brn3b and Math5, as assessed using by quantitative PCR and immunohistochemistry. The long, prominent axons contained neurofilaments and tau and exhibited anterograde axonal transport and sodium-dependent action potentials. The ability to generate RGCs with functional axons uniformly and at a high rate may contribute to both basic and clinical science, including embryology, neurology, pathognomy, and treatment of various optic nerve diseases that threaten vision.
authors: Department of Ophthalmology and Laboratory for Visual Science, National Centre for Child Health and Development, Tokyo, Japan.
authors: Taku
authors: T
authors: Tanaka
authors: Department of Ophthalmology and Laboratory for Visual Science, National Centre for Child Health and Development, Tokyo, Japan.
authors: Tadashi
authors: T
authors: Yokoi
authors: Department of Physiology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors: Fuminobu
authors: F
authors: Tamalu
authors: Department of Physiology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors: Shu-Ichi
authors: S
authors: Watanabe
authors: Department of Ophthalmology and Laboratory for Visual Science, National Centre for Child Health and Development, Tokyo, Japan.
authors: Sachiko
authors: S
authors: Nishina
authors: Department of Ophthalmology and Laboratory for Visual Science, National Centre for Child Health and Development, Tokyo, Japan.
authors: Noriyuki
authors: N
authors: Azuma
mesh_terms: D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D050820:Transcription Factor Brn-3B / Q000096:biosynthesis*
chemical_list: C494190:POU4F2 protein, human; D050820:Transcription Factor Brn-3B