ArticleInvestigative ophthalmology & visual science2024
Host-Graft Synapses Form Functional Microstructures and Shape the Host Light Responses After Stem Cell-Derived Retinal Sheet Transplantation.
Article in Investigative ophthalmology & visual science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Photoreceptor replacement: a disease-agnostic approach for the treatment of advanced retinal degeneration.Eye (London, England) · 2026Review
- Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Transplantation of human stem cell-derived cone photoreceptors partially restores vision in aged rd1 mice with advanced retinal degeneration.Stem cells (Dayton, Ohio) · 2026Article
- Cell therapy for age-related macular degeneration.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Production of clinical grade patient iPSC-derived 3D retinal organoids containing transplantable photoreceptor cells.Stem cell research & therapy · 2025Article
- Genome-edited retinal organoids restore host bipolar connectivity in the primate macula.bioRxiv : the preprint server for biology · 2025Article
- Graft-derived horizontal cells contribute to host-graft synapses in degenerated retinas after retinal organoid transplantation.Stem cell reports · 2025Article
- Animal models for the evaluation of retinal stem cell therapies.Progress in retinal and eye research · 2025Review
- Human cone photoreceptor transplantation stimulates remodeling and restores function in AIPL1 model of end-stage Leber congenital amaurosis.Stem cell reports · 2025Article
- Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.Stem cell reports · 2025Article
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Authors and funding
9 authors.
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Abstract
Purpose: Retinitis pigmentosa represents a leading cause of blindness in developed countries, yet effective treatments for the disease remain unestablished. Previous studies have demonstrated the potential of stem cell-derived retinal organoid (SC-RO) sheet transplantation to form host-graft synapses and to improve light responsiveness in animal models of retinal degeneration. However, the detailed microstructures of these de novo synapses and their functional contribution have not been well elucidated. This study aims to (1) elucidate the microstructures of the host-graft synapse, and (2) investigate the overall distribution and contribution of these synapses to host retinal light responses. Methods: We identified host-graft synapses using a reporter system in mouse SC-RO and rd1 mice, a well-established model of end-stage retinal degeneration. Correlative array tomography was used to reveal the microstructure of host-graft synapses. Furthermore, we developed a semi-automated algorithm that robustly detects the host-graft photoreceptor synapses in the overall grafted area using the same reporter system in flat-mount retinas. We then integrated the spatial distribution of the host-graft synapses with light responses detected by multi-electrode array recording. Results: Correlative array tomography revealed that host-graft synapses recapitulate the developmental process of photoreceptor synapse formation involving horizontal cells first and then rod bipolar cells. By integrating the spatial distribution of host-graft synapse and multi-electrode array recording, we showed that the number of light-responsive host retinal ganglion cells is positively correlated with the local density of host-graft synapses. Conclusions: De novo host-graft synapses recapitulate the developmental microstructure of the photoreceptor synapse, and their formation contributes to the light responsiveness after SC-RO transplantation.
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