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Generation of Retinal Organoids from Healthy and Retinal Disease-Specific Human-Induced Pluripotent Stem Cells
Published on: December 9, 2022
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Improved Retinal Organoid Differentiation by Modulating Signaling Pathways Revealed by Comparative Transcriptome
Matthew J Brooks1, Holly Y Chen1, Ryan A Kelley1
1Neurobiology-Neurodegeneration and Repair Laboratory, 6 Center Drive, MSC0610, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Stem Cell Reports
|October 22, 2019
Summary
Stem cell-derived retinal organoids show immature photoreceptors. Supplementation with docosahexaenoic acid and fibroblast growth factor 1 improved photoreceptor maturation, enhancing retinal organoid development for disease modeling.
Area of Science:
- Developmental Biology
- Stem Cell Research
- Neuroscience
- Ophthalmology
Background:
- Stem cell-derived retinal organoids mimic in vivo retinal development.
- However, they exhibit incomplete functional maturation, particularly in photoreceptor cells.
- This limits their utility for disease modeling and therapeutic research.
Purpose of the Study:
- To identify molecular and regulatory differences between developing mouse retina and retinal organoids.
- To investigate the reasons for the lack of photoreceptor functional maturation in organoids.
- To enhance the maturation of retinal organoids in vitro.
Main Methods:
- Comprehensive temporal transcriptome analyses of developing mouse retina and organoids.
- Co-expression network analysis to compare regulatory dynamics.
- Addition of docosahexaenoic acid and fibroblast growth factor 1 to organoid cultures.
Main Results:
- Retinal organoids lack the P6-P10 transcriptome shift crucial for mouse retina morphogenesis and synapse formation.
- Network analysis revealed divergent regulatory dynamics and dysregulated signaling pathways in organoids.
- Specific gene expression related to photoreceptor function and survival was delayed or reduced in organoids.
Conclusions:
- Retinal organoids are deficient in specific regulatory signals required for complete photoreceptor maturation.
- Supplementation with docosahexaenoic acid and fibroblast growth factor 1 promotes photoreceptor and cone maturation.
- This study provides a validated method for generating more mature retinal organoids for research.
