ArticleStem cell research & therapy2022
All-trans retinoic acid modulates pigmentation, neuroretinal maturation, and corneal transparency in human multiocular organoids.
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 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 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
- Review
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids.Nature communications · 2026Article
- Recurrent and persistent refractive errors after restarting isotretinoin treatment: a case report.Frontiers in pharmacology · 2026Article
- From Cells to Organoids: Approaches, Regulatory Mechanisms, Applications, and Challenges of Organoids.Cells · 2025Review
- Challenges and Advances in the Production of Transplantable Retinal Tissue from Retinal Organoids.Journal of ophthalmic & vision research · 2025Article
- Multi-omics study unravels gut microbiota and metabolites alteration in patients with Wilson's disease.Scientific reports · 2024Article
- Article
- All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia.Frontiers in pharmacology · 2024Review
- EYE-503: A Novel Retinoic Acid Drug for Treating Retinal Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases.International journal of molecular sciences · 2023Review
- All-trans retinoic acid regulates the expression of MMP-2 and TGF-β2International journal of ophthalmology · 2023Article
- A treatment within sight: challenges in the development of stem cell-derived photoreceptor therapies for retinal degenerative diseases.Frontiers in transplantation · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAll-trans retinoic acid (ATRA) plays an essential role during human eye development, being temporally and spatially adjusted to create gradient concentrations that guide embryonic anterior and posterior axis formation of the eye. Perturbations in ATRA signaling can result in severe ocular developmental diseases. Although it is known that ATRA is essential for correct eye formation, how ATRA influences the different ocular tissues during the embryonic development of the human eye is still not well studied. Here, we investigated the effects of ATRA on the differentiation and the maturation of human ocular tissues using an in vitro model of human-induced pluripotent stem cells-derived multiocular organoids.
methodsMultiocular organoids, consisting of the retina, retinal pigment epithelium (RPE), and cornea, were cultured in a medium containing low (500 nM) or high (10 µM) ATRA concentrations for 60 or 90 days. Furthermore, retinal organoids were cultured with taurine and T3 to further study photoreceptor modulation during maturation. Histology, immunochemistry, qPCR, and western blot were used to study gene and protein differential expression between groups.
resultsHigh ATRA levels promote the transparency of corneal organoids and the neuroretinal development in retinal organoids. However, the same high ATRA levels decreased the pigmentation levels of RPE organoids and, in long-term cultures, inhibited the maturation of photoreceptors. By contrast, low ATRA levels enhanced the pigmentation of RPE organoids, induced the opacity of corneal organoids-due to an increase in collagen type IV in the stroma- and allowed the maturation of photoreceptors in retinal organoids. Moreover, T3 promoted rod photoreceptor maturation, whereas taurine promoted red/green cone photoreceptors.
conclusionATRA can modulate corneal epithelial integrity and transparency, photoreceptor development and maturation, and the pigmentation of RPE cells in a dose-dependent manner. These experiments revealed the high relevance of ATRA during ocular tissue development and its use as a potential new strategy to better modulate the development and maturation of ocular tissue through temporal and spatial control of ATRA signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.