title: Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy.
abstract: Subretinal suspension transplants of human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) have the capacity to form functional monolayers in naive eyes. We explore hESC-RPE integration when transplanted in suspension to a large-eyed model of geographic atrophy (GA).
  
  
  
  Derivation of hESC-RPE was performed in a xeno-free and defined manner. Subretinal bleb injection of PBS or sodium iodate (NaIO3) was used to induce a GA-like phenotype. Suspensions of hESC-RPE were transplanted to the subretinal space of naive or PBS-/NaIO3-treated rabbits using a transvitreal pars plana technique. Integration of hESC-RPE was monitored by multimodal real-time imaging and by immunohistochemistry.
  
  
  
  Subretinal blebs of PBS or NaIO3 caused different degrees of outer neuroretinal degeneration, RPE hyperautofluorescence, focal RPE loss, and choroidal atrophy; that is, hallmark characteristics of GA. In nonpretreated naive eyes, hESC-RPE integrated as subretinal monolayers with preserved overlying photoreceptors, yet not in areas with outer neuroretinal degeneration and native RPE loss. When transplanted to eyes with PBS-/NaIO3-induced degeneration, hESC-RPE failed to integrate.
  
  
  
  In a large-eyed preclinical model, subretinal suspension transplants of hESC-RPE did not integrate in areas with GA-like degeneration.
authors.affiliation: Department of Clinical Neuroscience, Section for Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden 2Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden and Division of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Petrus-Reurer
authors.affiliation: Department of Clinical Neuroscience, Section for Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hammurabi
authors.initials: H
authors.lastname: Bartuma
authors.affiliation: Department of Clinical Neuroscience, Section for Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Monica
authors.initials: M
authors.lastname: Aronsson
authors.affiliation: Department of Clinical Neuroscience, Section for Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Westman
authors.affiliation: Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden and Division of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lanner
authors.affiliation: Department of Clinical Neuroscience, Section for Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helder
authors.initials: H
authors.lastname: André
authors.affiliation: Department of Clinical Neuroscience, Section for Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Kvanta
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000637:transplantation*; D057092:Geographic Atrophy / Q000628:therapy*; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D056965:Injections, Intraocular; D011817:Rabbits; D055213:Retinal Pigment Epithelium / Q000166:cytology*