Springer Nature

All-trans retinoic acid modulates pigmentation, neuroretinal maturation, and corneal transparency in human multiocular organoids

Posted on 2022-07-29 - 06:31
Abstract Background All-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. Methods Multiocular 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. Results High 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. Conclusion ATRA 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.


3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
AAPG Bulletin
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Select your citation style and then place your mouse over the citation text to select it.


need help?