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人干细胞来源的视网膜类器官在早期视网膜发育机制研究中的应用。

Application of Human Stem Cell Derived Retinal Organoids in the Exploration of the Mechanisms of Early Retinal Development.

机构信息

Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China.

出版信息

Stem Cell Rev Rep. 2023 Aug;19(6):1755-1772. doi: 10.1007/s12015-023-10553-x. Epub 2023 Jun 3.

Abstract

The intricate neural circuit of retina extracts salient features of the natural world and forms bioelectric impulse as the origin of vision. The early development of retina is a highly complex and coordinated process in morphogenesis and neurogenesis. Increasing evidence indicates that stem cells derived human retinal organoids (hROs) in vitro faithfully recapitulates the embryonic developmental process of human retina no matter in the transcriptome, cellular biology and histomorphology. The emergence of hROs greatly deepens on the understanding of early development of human retina. Here, we reviewed the events of early retinal development both in animal embryos and hROs studies, which mainly comprises the formation of optic vesicle and optic cup shape, differentiation of retinal ganglion cells (RGCs), photoreceptor cells (PRs) and its supportive retinal pigment epithelium cells (RPE). We also discussed the classic and frontier molecular pathways up to date to decipher the underlying mechanisms of early development of human retina and hROs. Finally, we summarized the application prospect, challenges and cutting-edge techniques of hROs for uncovering the principles and mechanisms of retinal development and related developmental disorder. hROs is a priori selection for studying human retinal development and function and may be a fundamental tool for unlocking the unknown insight into retinal development and disease.

摘要

视网膜的复杂神经网络提取自然世界的显著特征,并形成生物电冲动作为视觉的起源。视网膜的早期发育是形态发生和神经发生中高度复杂和协调的过程。越来越多的证据表明,体外培养的人视网膜类器官(hRO)中的干细胞忠实地再现了人类视网膜的胚胎发育过程,无论是在转录组、细胞生物学还是组织形态学上。hRO 的出现极大地加深了人们对人类视网膜早期发育的理解。在这里,我们回顾了动物胚胎和 hRO 研究中早期视网膜发育的事件,主要包括视囊和视杯形状的形成、视网膜神经节细胞(RGC)、光感受器细胞(PR)及其支持的视网膜色素上皮细胞(RPE)的分化。我们还讨论了迄今为止经典和前沿的分子途径,以破译人类视网膜和 hRO 早期发育的潜在机制。最后,我们总结了 hRO 用于揭示视网膜发育和相关发育障碍的原理和机制的应用前景、挑战和前沿技术。hRO 是研究人类视网膜发育和功能的先决选择,可能是深入了解视网膜发育和疾病的未知洞察力的基本工具。

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