ArticleStem cell research & therapy2022
Retinoic acid delays initial photoreceptor differentiation and results in a highly structured mature retinal organoid.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review.Stem cell reviews and reports · 2025Pooled it
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Long-term daily light exposure boosts human retinal organoid differentiation.Communications biology · 2026Article
- Single-cell analysis reveals impaired Müller glia-mediated intercellular communication and photoreceptor pathology in USH1C retinal organoids.Cellular and molecular life sciences : CMLS · 2026Article
- Retinal organoids: current status of development and new avenues for application in disease modeling, drug discovery and therapeutics.International journal of retina and vitreous · 2026Review
- Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids.Nature communications · 2026Article
- A cell fate specification and transition mechanism for human foveolar cone subtype patterning.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Graphene-polymer nanofibers enable optically induced electrical responses in stem cell-derived electrically excitable cells and brain organoids.Biomaterials · 2025Article
- Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing.Cellular and molecular life sciences : CMLS · 2025Review
- Human macula formation involves two waves of retinoic acid suppression via CYP26A1 that modulate cell cycle exit and cone subtype specification.Stem cell reports · 2025Article
- Genome-Wide Insights Into the Genes and Pathways Shaping Human Foveal Development: Redefining the Genetic Landscape of Foveal Hypoplasia.Investigative ophthalmology & visual science · 2025Article
- Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.International journal of molecular sciences · 2025Review
- The influence of SARS-CoV-2 spike protein exposure on retinal development in the human retinal organoids.Cell & bioscience · 2025Article
- Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration.International journal of molecular sciences · 2025Review
- Challenges and Advances in the Production of Transplantable Retinal Tissue from Retinal Organoids.Journal of ophthalmic & vision research · 2025Article
- Generation of Retinal Organoids Using Human-Induced Pluripotent Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.International journal of molecular sciences · 2024Article
- Dual CRALBP isoforms unveiled: iPSC-derived retinal modeling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman-induced pluripotent stem cell-derived retinal organoids are a valuable tool for disease modelling and therapeutic development. Many efforts have been made over the last decade to optimise protocols for the generation of organoids that correctly mimic the human retina. Most protocols use common media supplements; however, protocol-dependent variability impacts data interpretation. To date, the lack of a systematic comparison of a given protocol with or without supplements makes it difficult to determine how they influence the differentiation process and morphology of the retinal organoids.
methodsA 2D-3D differentiation method was used to generate retinal organoids, which were cultured with or without the most commonly used media supplements, notably retinoic acid. Gene expression was assayed using qPCR analysis, protein expression using immunofluorescence studies, ultrastructure using electron microscopy and 3D morphology using confocal and biphoton microscopy of whole organoids.
resultsRetinoic acid delayed the initial stages of differentiation by modulating photoreceptor gene expression. At later stages, the presence of retinoic acid led to the generation of mature retinal organoids with a well-structured stratified photoreceptor layer containing a predominant rod population. By contrast, the absence of retinoic acid led to cone-rich organoids with a less organised and non-stratified photoreceptor layer.
conclusionsThis study proves the importance of supplemented media for culturing retinal organoids. More importantly, we demonstrate for the first time that the role of retinoic acid goes beyond inducing a rod cell fate to enhancing the organisation of the photoreceptor layer of the mature organoid.
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