title: Characterization of a mouse model with complete RPE loss and its use for RPE cell transplantation.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement of RPE is discussed as a potential therapy for AMD. Previous studies were performed in animal models with severe limitations in recapitulating the disease progression. In detail, we describe the effect of systemic injection of sodium iodate in the mouse retina. We further evaluate the usefulness of this animal model to analyze cell-specific effects following transplantation of human embryonic stem cell (hESC)-derived RPE cells.
  
  
  METHODS
  Morphologic, functional, and behavioral changes following sodium iodate injection were monitored by histology, gene expression analysis, electroretinography, and optokinetic head tracking. Human embryonic stem cell-derived RPE cells were transplanted 1 week after sodium iodate injection and experimental retinae were analyzed 3 weeks later.
  
  
  RESULTS
  Injection of sodium iodate caused complete RPE cell loss, photoreceptor degeneration, and altered gene and protein expression in outer and inner nuclear layers. Retinal function was severely affected by day 3 and abolished from day 14. Following transplantation, donor hESC-derived RPE cells formed extensive monolayers that displayed wild-type RPE cell morphology, organization, and function, including phagocytosis of host photoreceptor outer segments.
  
  
  CONCLUSIONS
  Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nuclear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants. The availability of an RPE-free Bruch's membrane in this model likely allows the unprecedented formation of extensive polarized cell monolayers from donor hESC-derived RPE cell suspensions.
authors.affiliation: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
authors.forename: Madalena
authors.initials: M
authors.lastname: Carido
authors.affiliation: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Postel
authors.affiliation: Werner Reichardt Centre for Integrative Neuroscience and Bernstein Center for Computacional Biology, Universität Tübingen, Tübingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Benkner
authors.affiliation: Clinical Sensoring and Monitoring, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Cimalla
authors.affiliation: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany DZNE (German Center for Neurodegenerative Diseases), Dresden, Germany.
authors.forename: Mike O
authors.initials: MO
authors.lastname: Karl
authors.affiliation: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kurth
authors.affiliation: Institute for Ophthalmic Research, University of Tübingen, Germany.
authors.forename: François
authors.initials: F
authors.lastname: Paquet-Durand
authors.affiliation: Clinical Sensoring and Monitoring, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Edmund
authors.initials: E
authors.lastname: Koch
authors.affiliation: Werner Reichardt Centre for Integrative Neuroscience and Bernstein Center for Computacional Biology, Universität Tübingen, Tübingen, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Münch
authors.affiliation: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Tanaka
authors.affiliation: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ader
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D007452:Iodates / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000637:transplantation*
chemical_list: D007452:Iodates; C032285:sodium iodate
keywords: age-related macular degeneration; hESC-derived RPE; retinal pigment epithelium; sodium iodate; transplantation