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Transplanted pluripotent stem cell‐derived photoreceptor precursors elicit conventional and unusual light responses in mice with advanced retinal degeneration

Lookup NU author(s): Dr Darin Zerti, Dr Birthe HilgenORCiD, Dr Joseph Collin, Professor Lyle ArmstrongORCiD, Professor Evelyne SernagorORCiD, Professor Majlinda LakoORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

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.

Publication metadata

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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