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Organotypic Culture of Adult Rabbit Retina
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Genome-edited retinal organoids restore host bipolar connectivity in the primate macula
Atsuta Ozaki1,2,3, Akihiro Kawai4, Ryutaro Akiba4
1Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan.
Biorxiv : the Preprint Server for Biology
|September 5, 2025
Summary
Genome-edited retinal organoids successfully integrated with host cells in a primate model, restoring vision pathways. This breakthrough demonstrates the potential of stem cell therapy for macular degeneration.
Area of Science:
- Regenerative medicine
- Neuroscience
- Ophthalmology
Background:
- Retinal organoids offer potential for vision restoration in degenerative diseases.
- Host cone bipolar cell (BC) integration with transplanted photoreceptors in primates is not well understood.
Purpose of the Study:
- To investigate the rewiring capacity of host cone bipolar cells in the primate macula with transplanted photoreceptors.
- To assess functional synaptic integration after transplanting genome-edited retinal organoids lacking ON-BCs into a primate macular degeneration model.
Main Methods:
- Transplantation of genome-edited human retinal organoids (Islet-1⁻/⁻ ROs) into a non-human primate macular degeneration model.
- Confirmation of host-graft synaptic integration using immunohistochemistry, ultrastructural imaging, and focal macular electroretinography.
Main Results:
- Host rod and cone BCs extended dendrites to grafted photoreceptors.
- Functional synapses were formed, rebuilding both ON- and OFF-pathway connectivity.
- Demonstrated the first instance of host-graft synaptic integration in the primate macula.
Conclusions:
- Primate cone circuits exhibit significant rewiring capacity.
- Genome-edited ROs are a viable platform for vision restoration therapies.
- This research is a critical step towards stem cell-based treatments for advanced macular degeneration.
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