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Updated: Dec 27, 2025
Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases
Published on: June 14, 2021
Protective effects of human iPS-derived retinal pigmented epithelial cells on retinal degenerative disease
Deliang Zhu1,2, Mengyuan Xie1, Fabian Gademann2
1Key Laboratory of Optoelectronic Information and Sensing Technologies of Guangdong Higher Educational Institutes, Jinan University, Guangzhou, China.
Insights
Human induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) transplantation improved vision in a mouse model of retinitis pigmentosa. This cell therapy shows promise for treating inherited retinal diseases.
Area of Science:
- Stem cell biology
- Ophthalmology
- Regenerative medicine
Background:
- Retinitis pigmentosa (RP) is an inherited retinal disease causing progressive photoreceptor cell loss.
- The study investigates the therapeutic potential of human induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) in a mouse model of RP (rd10 mice).
Purpose of the Study:
- To evaluate the efficacy of subretinal transplantation of hiPSC-RPE cells in restoring retinal structure and function in rd10 mice.
- To assess the survival, integration, and therapeutic effects of transplanted hiPSC-RPE cells.
Main Methods:
- hiPSC-RPE cells were generated using sequential induction and optimized via 3D spheroid culture.
- Cells were transplanted into the subretinal space of rd10 mice.
- Therapeutic effects were assessed using immunostaining, ELISA, Western blotting, electroretinography (ERG), and visual behavior tests.
Main Results:
- Transplanted hiPSC-RPE cells survived, integrated, and exhibited RPE characteristics in the host retina.
- hiPSC-RPE transplantation reduced photoreceptor apoptosis and microglial activation.
- Significant improvements in visual function, including ERG responses and light avoidance behavior, were observed in treated rd10 mice.
Conclusions:
- Injectable hiPSC-RPE cells, cultured in 3D spheroids, can rescue photoreceptor structure and function following subretinal transplantation.
- This approach provides a foundation for clinical cell therapy strategies targeting RP and other retinal degenerative diseases.
Background:
Retinitis pigmentosa (RP) is an inherited retinal disease characterized by progressive loss of photoreceptor cells. This study aim at exploring the effect of retinal pigment epithelium (RPE) derived from human-induced pluripotent stem cell (hiPSC-RPE) on the retina of retinal degeneration 10 (rd10) mice, which are characterized with progressive photoreceptor death.
Methods:
We generated RPE from hiPSCs by sequential supplementation with retinal-inducing factors and RPE specification signaling factors. The three-dimensional (3D) spheroid culture method was used to obtain optimal injectable hiPSC-RPE cells. Subretinal space transplantation was conducted to deliver hiPSC-RPE cells into the retina of rd10 mice. Neurotrophic factor secretion from transplanted hiPSC-RPE cells was detected by enzyme-linked immunosorbent assay (ELISA). Immunostaining, Western blotting, electroretinography (ERG), and visual behavior testing were performed to determine the effects of hiPSC-RPE on the retinal visual function in rd10 mice.
Results:
Our data demonstrated that hiPSC-RPE cells exhibited classic RPE properties and phenotype after the sequential RPE induction from hiPSCs. hiPSC-RPE cells co-cultured with mouse retinal explants or retinal ganglion cells 5 (RGC5) exhibited decreased apoptosis. The viability and functional properties of hiPSC-RPE cells were enhanced by 3D spheroid culture. Transplanted hiPSC-derived RPE cells were identified by immunostaining with human nuclear antigen staining in the retina of rd10 14 days after subretinal space injection. The pigment epithelium-derived factor level was increased significantly. The expression of CD68, microglial activation marker, reduced after transplantation. The light avoidance behavior and ERG visual function in rd10 mice improved by the transplantation of hiPSC-RPE cells.
Conclusion:
Our findings suggest that injectable hiPSC-RPE cells after 3D spheroid culture can rescue the structure and function of photoreceptors by sub-retinal transplantation, which lay the foundation for future clinical cell therapy to treat RP and other retinal degeneration diseases.
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