Restoration of vision after transplantation of photoreceptors.

TitleRestoration of vision after transplantation of photoreceptors.
Publication TypeJournal Article
Year of Publication2012
AuthorsPearson RA, Barber AC, Rizzi M, Hippert C, Xue T, West EL, Duran Y, Smith AJ, Chuang JZ, Azam SA, Luhmann UFO, Benucci A, Sung CH, Bainbridge JW, Carandini M, Yau K-W, Sowden JC, Ali RR
JournalNature
Volume485
Issue7396
Pagination99-103
Date Published2012 May 03
ISSN1476-4687
KeywordsAnimals, GTP-Binding Protein alpha Subunits, Light, Maze Learning, Mice, Retinal Bipolar Cells, Retinal Horizontal Cells, Retinal Rod Photoreceptor Cells, Transducin, Vision, Ocular, Visual Cortex
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.

DOI10.1038/nature10997
Alternate JournalNature
PubMed ID22522934
PubMed Central IDPMC3888831
Grant ListR01 EY006837 / EY / NEI NIH HHS / United States
EY11307 / EY / NEI NIH HHS / United States
NIHR-RP-011-003 / / Department of Health / United Kingdom
G0800791 / / Medical Research Council / United Kingdom
EY016805 / EY / NEI NIH HHS / United States
R01 EY016805 / EY / NEI NIH HHS / United States
R01 EY011307-18 / EY / NEI NIH HHS / United States
/ / Department of Health / United Kingdom
R37 EY006837 / EY / NEI NIH HHS / United States
G0700438 / / Medical Research Council / United Kingdom
082217 / / Wellcome Trust / United Kingdom
R01 EY016805-07 / EY / NEI NIH HHS / United States
EY06837 / EY / NEI NIH HHS / United States
G03000341 / / Medical Research Council / United Kingdom
R01 EY011307 / EY / NEI NIH HHS / United States
F32 EY006837 / EY / NEI NIH HHS / United States
G0901550 / / Medical Research Council / United Kingdom
MR/J004553/1 / / Medical Research Council / United Kingdom