Details

Autor(en) / Beteiligte

• Zerti, Darin
• Hilgen, Gerrit
• Dorgau, Birthe
• Collin, Joseph
• Ader, Marius
• Armstrong, Lyle
• Sernagor, Evelyne
• Lako, Majlinda

Titel

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

Ist Teil von

• Stem cells (Dayton, Ohio), 2021-07, Vol.39 (7), p.882-896

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2021

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. This study assessed the ability of pluripotent stem cell derived cone photoreceptors to engraft in an end‐stage mouse model of photoreceptor degeneration model and restore vision. Our data demonstrate that pluripotent stem cell derived cone precursors can engraft into the host retina 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 light responses and motion sensitivity, however quite a few exhibited unusual responses reflecting remodelling of the neural retina. Together these data suggest that pluripotent stem cell‐derived cone precursors can elicit conventional and unusual light responsiveness at advanced degeneration stages.