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Lookup NU author(s): Dr Darin Zerti, Dr Birthe HilgenORCiD, Dr Joseph Collin, Professor Lyle Armstrong, Professor Evelyne SernagorORCiD, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Retinal dystrophies often lead to blindness. Developing therapeutic interventions to restore vision is therefore of paramount importance. Here we demonstrate the ability of pluripotent stem cell-derived cone precursors to engraft and restore light responses in the Pde6brd1 mouse, an end-stage photoreceptor degeneration model. Our data show that up to 1.5% of precursors integrate into the host retina, differentiate into cones, and engraft in close apposition to the host bipolar cells. Half of the transplanted mice exhibited visual behaviour and of these 33% showed binocular light sensitivity. The majority of retinal ganglion cells (RGCs) exhibited contrast-sensitive ON, OFF or ON-OFF light responses and even motion sensitivity, however quite a few exhibited unusual responses (e.g., light-induced suppression), presumably reflecting remodelling of the neural retina. Our data indicate that despite relatively low engraftment yield, pluripotent stem cell-derived cone precursors can elicit light responsiveness even at advanced degeneration stages. Further work is needed to improve engraftment yield and counteract retinal remodelling to achieve useful clinical applications.
Author(s): Zerti D, Hilgen G, Dorgau b, Collin J, Ader M, Armstrong L, Sernagor E, Lako M
Publication type: Article
Publication status: Published
Journal: Stem Cells
Year: 2021
Volume: 39
Issue: 7
Pages: 882-896
Print publication date: 01/07/2021
Online publication date: 03/03/2021
Acceptance date: 19/02/2021
Date deposited: 08/04/2021
ISSN (print): 1066-5099
ISSN (electronic): 1549-4918
Publisher: AlphaMed Press
URL: https://doi.org/10.1002/stem.3365
DOI: 10.1002/stem.3365
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