Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis IN, USA.
Interdisciplinary Biomedical Research Gateway Program, Indiana University School of Medicine, Indianapolis IN, USA; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis IN, USA.
Stem Cell Reports. 2021 Sep 14;16(9):2228-2241. doi: 10.1016/j.stemcr.2021.05.009. Epub 2021 Jun 10.
The development of the visual system involves the coordination of spatial and temporal events to specify the organization of varied cell types, including the elongation of axons from retinal ganglion cells (RGCs) to post-synaptic targets in the brain. Retinal organoids recapitulate many features of retinal development, yet have lacked downstream targets into which RGC axons extend, limiting the ability to model projections of the human visual system. To address these issues, retinal organoids were generated and organized into an in vitro assembloid model of the visual system with cortical and thalamic organoids. RGCs responded to environmental cues and extended axons deep into assembloids, modeling the projections of the visual system. In addition, RGC survival was enhanced in long-term assembloids, overcoming prior limitations of retinal organoids in which RGCs are lost. Overall, these approaches will facilitate studies of human visual system development, as well as diseases or injuries to this critical pathway.
视觉系统的发育涉及空间和时间事件的协调，以确定各种细胞类型的组织，包括视网膜神经节细胞（RGC）的轴突向大脑中的突触后靶区的延伸。视网膜类器官再现了视网膜发育的许多特征，但缺乏 RGC 轴突延伸的下游靶标，限制了对人类视觉系统投射进行建模的能力。为了解决这些问题，生成了视网膜类器官，并将其组织成具有皮质和丘脑类器官的体外集合体模型。RGC 对环境线索作出反应，并将轴突深入延伸到集合体中，从而模拟了视觉系统的投射。此外，在长期的集合体中，RGC 的存活得到了增强，克服了以前视网膜类器官中 RGC 丢失的局限性。总的来说，这些方法将促进对人类视觉系统发育以及该关键途径的疾病或损伤的研究。
