Journal
STEM CELLS
Volume 39, Issue 7, Pages 882-896Publisher
OXFORD UNIV PRESS
DOI: 10.1002/stem.3365
Keywords
multielectrode arrays; multielectrode recordings; Pde6brd1; photoreceptors; pluripotent stem cells; retinal degenerative diseases; retinal ganglion cells; retinal remodeling; retinitis pigmentosa; subretinal transplantation
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Funding
- ERC [614620]
- RP Fighting Blindness [GR593]
- Leverhulme Trust [RPG-2016-315]
- BBSRC [BB/P018440/1]
- BBSRC [BB/P018440/1] Funding Source: UKRI
- European Research Council (ERC) [614620] Funding Source: European Research Council (ERC)
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The study demonstrates the ability of pluripotent stem cell-derived cone precursors to engraft and restore light responses in a mouse model of end-stage photoreceptor degeneration. While half of the transplanted mice exhibited improved visual behavior, some retinal ganglion cells showed unusual responses, indicating the need for further research to improve engraftment yield and counteract retinal remodeling for clinical applications.
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 behavior and of these 33% showed binocular light sensitivity. The majority of retinal ganglion cells exhibited contrast-sensitive ON, OFF or ON-OFF light responses and even motion sensitivity; however, quite a few exhibited unusual responses (eg, light-induced suppression), presumably reflecting remodeling 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 remodeling to achieve useful clinical applications.
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