Transplanted Mouse Embryonic Stem Cell-Derived Retinal Ganglion Cells Integrate and Form Synapses in a Retinal Ganglion Cell-Depleted Mouse Model

移植小鼠胚胎干细胞衍生的视网膜神经节细胞在视网膜神经节细胞耗尽的小鼠模型中整合并形成突触

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作者:You-Ren Wu, Tomoyo Hashiguchi, Junki Sho, Shih-Hwa Chiou, Masayo Takahashi, Michiko Mandai

Conclusions

This report shows the potential for therapeutic use of pluripotent cell-derived RGCs by grafting the cells in healthy conditions and with an appropriate technical approach.

Methods

In this study, we prepared small retinal fragments containing RGC as THY1-enhanced green fluorescent protein (EGFP)+ cells from mESCs and placed them near the retinal surface in the air-injected mouse eyes with or without N-methyl-d-aspartate (NMDA)-induced RGC depletion. After transplantation, THY1-EGFP+ cell integration was observed in whole-mounts and with immunostaining for synaptic markers.

Purpose

Retinal ganglion cell (RGC) transplantation is a therapeutic approach to replace irreversibly degenerated RGCs in diseases such as glaucoma. However, the application of primary RGCs is limited by the availability of tissues. The goal of this study was to evaluate whether transplanted mouse embryonic stem cell (mESC)-derived RGCs can integrate into the host retina and form cell connectivity with host cells.

Results

Transplanted THY1-EGFP+ cells survived for 12 weeks and extended neurites into the inner plexiform layer (IPL) of the host retina. Presumptive synapse formation was identified between grafted RGCs and host bipolar cells. The ratio of transplanted eyes with integration of THY1-EGFP+ neurites in the host IPL was higher in RGC-injured mice compared with healthy controls. Conclusions: This report shows the potential for therapeutic use of pluripotent cell-derived RGCs by grafting the cells in healthy conditions and with an appropriate technical approach.

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