title: iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice.
abstract: Recent success in functional recovery by photoreceptor precursor transplantation in dysfunctional retina has led to an increased interest in using embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal progenitors to treat retinal degeneration. However, cell-based therapies for end-stage degenerative retinas that have lost the outer nuclear layer (ONL) are still a big challenge. In the present study, by transplanting mouse iPSC-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model (rd1), we visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system. Our data provides a proof of concept for transplanting ESC/iPSC retinas to restore vision in end-stage retinal degeneration.
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: mmandai@cdb.riken.jp.
authors.forename: Michiko
authors.initials: M
authors.lastname: Mandai
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Momo
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hashiguchi
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Genshiro A
authors.initials: GA
authors.lastname: Sunagawa
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Shin-ichiro
authors.initials: SI
authors.lastname: Ito
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Jianan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kaneko
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Sho
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Yamada
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D002450:Cell Communication; D002454:Cell Differentiation; D055724:Electrophysiological Phenomena; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D012038:Regeneration; D012160:Retina / Q000166:cytology* / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000378:metabolism; D012162:Retinal Degeneration / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D033581:Stem Cell Transplantation; D013570:Synaptic Membranes / Q000378:metabolism
keywords: iPSC; multiple electrode array; photoreceptor transplantation; retinal degeneration; retinal regeneration; shuttle-avoidance test