title: Restoration of vision after transplantation of photoreceptors.
abstract: Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, University College London, 11–43 Bath Street, London, EC1V 9EL, UK. rachael.pearson@ucl.ac.uk
authors.forename: R A
authors.initials: RA
authors.lastname: Pearson
authors.forename: A C
authors.initials: AC
authors.lastname: Barber
authors.forename: M
authors.initials: M
authors.lastname: Rizzi
authors.forename: C
authors.initials: C
authors.lastname: Hippert
authors.forename: T
authors.initials: T
authors.lastname: Xue
authors.forename: E L
authors.initials: EL
authors.lastname: West
authors.forename: Y
authors.initials: Y
authors.lastname: Duran
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
authors.forename: J Z
authors.initials: JZ
authors.lastname: Chuang
authors.forename: S A
authors.initials: SA
authors.lastname: Azam
authors.forename: U F O
authors.initials: UF
authors.lastname: Luhmann
authors.forename: A
authors.initials: A
authors.lastname: Benucci
authors.forename: C H
authors.initials: CH
authors.lastname: Sung
authors.forename: J W
authors.initials: JW
authors.lastname: Bainbridge
authors.forename: M
authors.initials: M
authors.lastname: Carandini
authors.forename: K-W
authors.initials: KW
authors.lastname: Yau
authors.forename: J C
authors.initials: JC
authors.lastname: Sowden
authors.forename: R R
authors.initials: RR
authors.lastname: Ali
mesh_terms: D000818:Animals; D044385:GTP-Binding Protein alpha Subunits / Q000172:deficiency / Q000235:genetics; D008027:Light; D018782:Maze Learning; D051379:Mice; D051245:Retinal Bipolar Cells / Q000648:ultrastructure; D051248:Retinal Horizontal Cells / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects / Q000637:transplantation*; D015293:Transducin / Q000172:deficiency / Q000235:genetics; D014785:Vision, Ocular / Q000502:physiology* / Q000528:radiation effects; D014793:Visual Cortex / Q000502:physiology / Q000528:radiation effects
chemical_list: D044385:GTP-Binding Protein alpha Subunits; C488949:Gnat1 protein, mouse; D015293:Transducin