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      Retinal organoids: a window into human retinal development

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          ABSTRACT

          Retinal development and maturation are orchestrated by a series of interacting signalling networks that drive the morphogenetic transformation of the anterior developing brain. Studies in model organisms continue to elucidate these complex series of events. However, the human retina shows many differences from that of other organisms and the investigation of human eye development now benefits from stem cell-derived organoids. Retinal differentiation methods have progressed from simple 2D adherent cultures to self-organising micro-physiological systems. As models of development, these have collectively offered new insights into the previously unexplored early development of the human retina and informed our knowledge of the key cell fate decisions that govern the specification of light-sensitive photoreceptors. Although the developmental trajectories of other retinal cell types remain more elusive, the collation of omics datasets, combined with advanced culture methodology, will enable modelling of the intricate process of human retinogenesis and retinal disease in vitro.

          Abstract

          Summary: Retinal organoid systems derived from human pluripotent stem cells are micro-physiological systems that offer new insights into previously unexplored human retina development.

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          Most cited references161

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          Reconstituting organ-level lung functions on a chip.

          Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.
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            Self-organizing optic-cup morphogenesis in three-dimensional culture.

            Balanced organogenesis requires the orchestration of multiple cellular interactions to create the collective cell behaviours that progressively shape developing tissues. It is currently unclear how individual, localized parts are able to coordinate with each other to develop a whole organ shape. Here we report the dynamic, autonomous formation of the optic cup (retinal primordium) structure from a three-dimensional culture of mouse embryonic stem cell aggregates. Embryonic-stem-cell-derived retinal epithelium spontaneously formed hemispherical epithelial vesicles that became patterned along their proximal-distal axis. Whereas the proximal portion differentiated into mechanically rigid pigment epithelium, the flexible distal portion progressively folded inward to form a shape reminiscent of the embryonic optic cup, exhibited interkinetic nuclear migration and generated stratified neural retinal tissue, as seen in vivo. We demonstrate that optic-cup morphogenesis in this simple cell culture depends on an intrinsic self-organizing program involving stepwise and domain-specific regulation of local epithelial properties. ©2011 Macmillan Publishers Limited. All rights reserved
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              Self-formation of optic cups and storable stratified neural retina from human ESCs.

              In this report, we demonstrate that an optic cup structure can form by self-organization in human ESC culture. The human ESC-derived optic cup is much larger than the mouse ESC-derived one, presumably reflecting the species differences. The neural retina in human ESC culture is thick and spontaneously curves in an apically convex manner, which is not seen in mouse ESC culture. In addition, human ESC-derived neural retina grows into multilayered tissue containing both rods and cones, whereas cone differentiation is rare in mouse ESC culture. The accumulation of photoreceptors in human ESC culture can be greatly accelerated by Notch inhibition. In addition, we show that an optimized vitrification method enables en bloc cryopreservation of stratified neural retina of human origin. This storage method at an intermediate step during the time-consuming differentiation process provides a versatile solution for quality control in large-scale preparation of clinical-grade retinal tissues. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Development
                Development
                DEV
                develop
                Development (Cambridge, England)
                The Company of Biologists Ltd
                0950-1991
                1477-9129
                15 December 2020
                24 December 2020
                24 December 2020
                : 147
                : 24
                : dev189746
                Affiliations
                [1 ]Stem Cell Medicine Group, Children's Medical Research Institute, University of Sydney , Westmead, 2145, NSW, Australia
                [2 ]School of Medical Sciences , Faculty of Medicine and Health, University of Sydney , Westmead, 2145, NSW, Australia
                Author notes
                [* ]Author for correspondence ( agonzalez-cordero@ 123456cmri.org.au )
                Author information
                http://orcid.org/0000-0002-2467-3790
                http://orcid.org/0000-0002-1818-0375
                Article
                DEV189746
                10.1242/dev.189746
                7774906
                33361444
                22d33338-cc28-4ee3-9a97-d1fbdfa24e84
                © 2020. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                Funding
                Funded by: New South Wales Luminesce Alliance;
                Award ID: PPM1 K5116/RD274
                Categories
                210
                Review

                Developmental biology
                retinal organoids,stem cells,human development
                Developmental biology
                retinal organoids, stem cells, human development

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