Genetically engineered stem cell-derived retinal grafts for improved retinal reconstruction after transplantation
Take Matsuyama,
Hung-Ya Tu,
Jianan Sun,
Tomoyo Hashiguchi,
Ryutaro Akiba,
Junki Sho,
Momo Fujii,
Akishi Onishi,
Masayo Takahashi,
Michiko Mandai
Affiliations
Take Matsuyama
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Hyogo, Japan
Hung-Ya Tu
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, Japan
Jianan Sun
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Tomoyo Hashiguchi
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Ryutaro Akiba
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Junki Sho
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Momo Fujii
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Akishi Onishi
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Masayo Takahashi
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Hyogo, Japan
Michiko Mandai
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Hyogo, Japan; Corresponding author
Summary: ESC/iPSC-retinal sheet transplantation, which supplies photoreceptors as well as other retinal cells, has been shown to be able to restore visual function in mice with end-stage retinal degeneration. Here, by introducing a novel type of genetically engineered mouse ESC/iPSC-retinal sheet with reduced numbers of secondary retinal neurons but intact photoreceptor cell layer structure, we reinforced the evidence that ESC/iPSC-retinal sheet transplantation can establish synaptic connections with the host, restore light responsiveness, and reduce aberrant retinal ganglion cell spiking in mice. Furthermore, we show that genetically engineered grafts can substantially improve the outcome of the treatment by improving neural integration. We speculate that this leads to reduced spontaneous activity in the host which in turn contributes to a better visual recovery.
