China
Africa
Explore chapters and articles related to this topic
The Developmental Toxicity of Metals and Metalloids in Fish
Published in Michael C. Newman, Alan W. McIntosh, Metal Ecotoxicology, 2020
Fish embryos, in general, tend to become abnormal in certain ways. The most sensitive system appears to be the developing skeletal system, and flexures (scoliosis, lordosis), as well as stunting, are seen in many species treated with a variety of teratogens. Another common set of abnormalities involves the developing circulatory system. Circulatory stasis, a failure of the heart tube to bend, and edema of the pericardial cavity are also commonly observed defects. The developing optic system is also very sensitive, and many investigators have observed optic malformations, such as microphthalmia and anophthalmia, as well as cyclopia and intermediate conditions of fusion of the two optic vesicles (synophthalmia). Again, these tend to be nonspecific responses; the appearance of a certain syndrome in a certain species of fish cannot, in general, be used to diagnose the presence of a specific teratogen.
Organoid Technology for Basic Science and Biomedical Research
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Szu-Hsien (Sam) Wu, Jihoon Kim, Bon-Kyoung Koo
The retina is the neural region of the eye which responds to stimulation by light. During development, the optic vesicle evaginates from the pseudostratified neuroepithelium and the distal part invaginates to form the optic cup. To explore the dynamics of cellular interaction and behavior, Sasai et al. (Eiraku et al. 2011) utilized the SFEBq mESC culture with Matrigel in order to generate a self-organizing optic cup. The resulting organoids expressed markers found in the developing retina and recapitulated in vivo development (Eiraku et al. 2011). Using a similar approach with some further optimization, optic cup organoids could also be generated from human PSCs. Interestingly, the hPSC-derived optic cup organoids grew to a larger size and formed multi-layered tissue containing rod and cone cells, thus recapitulating species-specific features of development (Nakano et al. 2012).
Modeling Neuroretinal Development and Disease in Stem Cells
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
A seminal work came out of the Sasai lab using mESCs to generate self-organizing optic cups (Eiraku et al., 2011; Eiraku and Sasai, 2012) (Figure 11.4). The authors described a methodology to differentiate ESCs in low-attachment plates in order to allow them to self-organize. Within a matter of a week, vesicle-like extensions protruded from the sides of the 3D cultures. The authors used an Rx-green fluorescent protein (GFP) line to easily identify these structures, which could then be pinched off. The optic vesicles then matured to form bilayered optic cups as in the embryo such that the outer layer formed MITF+ RPE and the inner layer differentiated into VSX2+ neural retina. The neural retina subsequently matured to form a multilaminated retina with appropriately oriented photoreceptor layer and inner retina. This was soon followed by another report by the group showing that the process can be reproduced in hESCs as well (Nakano et al., 2012). The authors used ROCK pathway inhibitor to allow single-cell survival and Wnt pathway inhibitor, IWR-1-endo, promote optic vesicle formation. To further promote neural retinal formation, the 3D clusters were treated with 10% fetal bovine serum and Hedgehog pathway component smoothened agonist. Interestingly, the addition of a small-molecule Wnt agonist at this stage of the protocol promoted RPE over the neuroretinal fate in the optic cups. Upon further differentiation for over 120+ days in 3D low-attachment conditions, the tissue formed a multi-laminated retina with the presence of all major cell types including rods, cones, retinal interneurons, and RGCs in mostly the right layers. The addition of a small-molecule Notch pathway inhibitor promoted stage-specific synchronized differentiation. The group recently published a report showing that the addition of BMP4 from days 6–15 of the protocol enhanced neuroretinal fate in these cells and prevented Foxg1+ telencephalic neuroepithelium induction (Kuwahara et al., 2015). The addition of glycogen synthase kinase 3 inhibitors along with FGF receptor inhibitors from days 18–24 promoted RPE fates and could be reversed by the change of media back to that containing retinoic acid and taurine. A very recent report analyzed the ability of these 3D spheres to integrate in immune-deficient nude rats and in two primate models of retinal degeneration (Shirai et al., 2016). The primate models were generated either by subretinal injection of cobalt chloride or by laser photocoagulation. Although the authors reported that the grafted hESC retina was observed differentiating into various retinal neuron subtypes, including rod and cone photoreceptors following transplantation, the integration appeared to be limited at the sites of apposition only. The photoreceptors tended to stay in the sphere and not migrate into the host retina.
Embryotoxic effects of Rovral® for early chicken (Gallus gallus) development
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Beatriz Mitidiero Stachissini Arcain, Maria Cláudia Gross, Danúbia Frasson Furtado, Carla Vermeulen Carvalho Grade
Ocular development starts from a signaling cascade between surface and diencephalon ectoderm, which forms the optic vesicle, in a complex process involving several signaling molecules (Zuber et al. 2003). In early embryonic stages lack of bone morphogenic protein (BMP) signaling, by overexpression of BMP binding protein noggin, as well as defective expression of microphthalmia-associated transcription factor (MITF) lead to microphthalmia (Adler and Belecky-Adams 2002), as was observed for some embryos (n = 6) treated with Rovral®. Alterations in the expression of Sox2 have also been connected to microphthalmia as well as anophthalmia, a condition detected in one embryo treated with Rovral®. Cases of microphthalmia were previously reported in other species contaminated by pesticides (Mishra and Devi 2014; Quintaneiro, Soares, and Monteiro 2018; Sabir et al. 2015; Soni et al. 2011; Yashwanth, Pamanji, and Rao 2016). Further studies are needed to determine how Rovral® affects regulation of signaling pathways leading to eye formation.