iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice

Mandai, Michiko; Fujii, Momo; Hashiguchi, Tomoyo; Sunagawa, Genshiro A.; Ito, Shinichiro; Sun, Jianan; Kaneko, Jun; Sho, Junki; Yamada, Chikashi; Takahashi, Masayo

doi:10.1016/j.stemcr.2017.03.024

Cited by 80 publications

(107 citation statements)

References 5 publications

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“…For example, retinal sheets have been derived from mouse embryonic stem cells (ESCs) or mouse iPSCs using a modified optic cup organoid protocol 12 and transplanted into a mouse model of retinal degeneration. The transplanted tissue gave rise to mature photoreceptors and, in some cases, established synaptic connections with the host cells 110 and recovered light responsiveness 111 . Retinal tissues generated from human ESC-derived organoids also survive, mature and demonstrate a degree of integration with the host tissue when transplanted into rat and primate models of retinal degeneration 112 .…”

Section: Regenerative Medicinementioning

confidence: 99%

Progress and potential in organoid research

2018

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Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns. However, advances in stem cell culture have made it possible to derive in vitro 3D tissues called organoids, which capture some of the key multicellular, anatomical and even functional hallmarks of real organs at the micrometre to millimetre scale. Recent studies have demonstrated that organoids can be used to model organ development and disease and have a wide range of applications in basic research, drug discovery and regenerative medicine. Researchers are now beginning to take inspiration from other fields, such as bioengineering, to generate organoids that are more physiologically relevant and more amenable to real-life applications.

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Section: Regenerative Medicinementioning

confidence: 99%

Progress and potential in organoid research

2018

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“…In addition to phototransduction proteins, donor‐derived GFP was shown to participate in ME prompting a reinterpretation of the extent of donor‐host connectivity reported in previous studies. Bona fide synaptic integration of donor photoreceptors with the host retinal circuitry is limited in retinal transplants , which is speculated to be because of the absence or abundance of appropriate permissive or inhibitory cues, respectively.…”

Section: Introductionmentioning

confidence: 99%

Modeling of Photoreceptor Donor-Host Interaction Following Transplantation Reveals a Role for Crx, Müller Glia, and Rho/ROCK Signaling in Neurite Outgrowth

et al. 2019

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The goal of photoreceptor transplantation is to establish functional synaptic connectivity between donor cells and second-order neurons in the host retina. There is, however, limited evidence of donor-host photoreceptor connectivity post-transplant. In this report, we investigated the effect of the host retinal environment on donor photoreceptor neurite outgrowth in vivo and identified a neurite outgrowth-promoting effect of host Crx (−/−) retinas following transplantation of purified photoreceptors expressing green fluorescent protein (GFP). To investigate the noncell autonomous factors that influence donor cell neurite outgrowth in vitro, we established a donor-host coculture system using postnatal retinal aggregates. Retinal cell aggregation is sensitive to several factors, including plate coating substrate, cell density, and the presence of Müller glia. Donor photoreceptors exhibit motility in aggregate cultures and can engraft into established aggregate structures. The neurite outgrowth-promoting phenotype observed in Crx (−/−) recipients in vivo is recapitulated in donor-host aggregate cocultures, demonstrating the utility of this surrogate in vitro approach. The removal of Müller glia from host aggregates reduced donor cell neurite outgrowth, identifying a role for this cell type in donor-host signaling. Although disruption of chondroitin sulfate proteoglycans in aggregates had no effect on the neurite outgrowth of donor photoreceptors, disruption of Rho/ROCK signaling enhanced outgrowth. Collectively, these data show a novel role of Crx, Müller glia, and Rho/ROCK signaling in controlling neurite outgrowth and provide an accessible in vitro model that can be used to screen for factors that regulate donor-host connectivity. STEM CELLS 2019;37:529-541 SIGNIFICANCE STATEMENTPoor photoreceptor connectivity in transplants is an unresolved issue. Results of the study show that photoreceptor neurite extension is regulated by Rho/ROCK signaling and report the use of primary retinal cultures as an in vitro platform to investigate donor photoreceptor neurite outgrowth. The results could be used in future work to enhance the connectivity of transplanted photoreceptors.

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“…Hierfür sind insbesondere visusabhängige Verhaltenstests erforderlich, wie z. B. das von der Sehfähigkeit abhängige Morris-Wasserlabyrinth [37] oder der "Shuttle-Avoidence-Test" [75]. Die Effektivität einer Photorezeptorersatztherapie wird hier insbesondere von der Menge an Spenderzellen abhängen, die korrekte und funktionale synaptische Verbindungen mit endogenen Nervenzellen aufbauen.…”

Section: Zytoplasmatischer Materialtransfer Vs Strukturelle Integrationunclassified

Photorezeptortransplantation in die degenerative Netzhaut

Borsch

Santos-Ferreira

Ader

2017

Klin Monatsbl Augenheilkd

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EinleitungDie Netzhaut des Auges erlaubt die Detektion von Licht und vermittelt damit die Fähigkeit, die uns umgebende Welt visuell wahrzunehmen. Die lichtsensitiven Zellen der Netzhaut -Stäbchen-und Zapfenphotorezeptoren -sind die erste Station der visuellen Wahrnehmung und essenziell für den Sehprozess. Sie vermitteln die Umwandlung der physikalischen Lichtsignale in veränderte Membranpotenziale, welche die Ausschüttung des Neurotransmitters Glutamat an der Synapse regulieren. Verschiedene Erkrankungen, wie Retinitis pigmentosa (RP), Leberʼsche kongenitale

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iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice

Cited by 80 publications

References 5 publications

Progress and potential in organoid research

Progress and potential in organoid research

Modeling of Photoreceptor Donor-Host Interaction Following Transplantation Reveals a Role for Crx, Müller Glia, and Rho/ROCK Signaling in Neurite Outgrowth

Photorezeptortransplantation in die degenerative Netzhaut

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