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Updated: Oct 23, 2025
Author Spotlight: Advancing Vision Restoration - Stem Cell-Based Therapy for Retinal Diseases
Published on: October 6, 2023
cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human
Swathi Lingam1,2, Zengping Liu1,2,3, Binxia Yang1
1Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
Background:
Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs).
Methods:
Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells.
Results:
There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation.
Conclusions:
These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials.
Insights
Induced pluripotent stem cell-derived photoreceptor precursors showed safety and therapeutic potential in non-human primates. These retinal regenerative therapies may offer future treatments for inherited retinal degenerations.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Inherited retinal degenerations (IRDs) are a target for regenerative therapies.
- Preclinical studies show promise, but higher mammal data is limited.
- Evaluating induced pluripotent stem cells (iPSCs) for retinal repair is crucial.
Purpose of the Study:
- Assess the therapeutic potential of iPSC-derived photoreceptor precursors.
- Evaluate safety and efficacy in a higher mammal model.
Main Methods:
- Sub-retinal transplantation of photoreceptor precursors into non-human primates (Macaca fascicularis).
- Used both naïve and cobalt chloride-induced retinal degeneration models.
- Employed optical coherence tomography, fundus autofluorescence, electroretinography, histology, and immunofluorescence.
Main Results:
- iPSC-derived photoreceptor precursors were biocompatible in naïve models.
- Transplanted cells survived and matured into cone photoreceptors in degeneration models.
- Optical coherence tomography revealed restoration of the retinal ellipsoid zone.
Conclusions:
- iPSC-derived photoreceptor precursors are safe and effective for retinal repair.
- Demonstrated potential for cell replacement therapy in IRDs.
- Supports clinical trial development for inherited retinal degenerations.
