Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China.
Key Lab of Visual Damage and Regeneration &Restoration of Chongqing, Chongqing 400038, China.
Sci Rep. 2016 Jul 20;6:29944. doi: 10.1038/srep29944.
The vertebrate retina is a highly multilayered nervous tissue with a large diversity of cellular components. With the development of stem cell technologies, human retinas can be generated in three-dimensional (3-D) culture in vitro. However, understanding the factors modulating key productive processes and the way that they influence development are far from clear. Oxygen, as the most essential element participating in metabolism, is a critical factor regulating organic development. In this study, using 3-D culture of human stem cells, we examined the effect of intermittent high oxygen treatment (40% O2) on the formation and cellular behavior of neural retinas (NR) in the embryonic body (EB). The volume of EB and number of proliferating cells increased significantly under 40% O2 on day 38, 50, and 62. Additionally, the ratio of PAX6+ cells within NR was significantly increased. The neural rosettes could only develop with correct apical-basal polarity under 40% O2. In addition, the generation, migration and maturation of retinal ganglion cells were enhanced under 40% O2. All of these results illustrated that 40% O2 strengthened the formation of NR in EB with characteristics similar to the in vivo state, suggesting that the hyperoxic state facilitated the retinal development in vitro.
脊椎动物的视网膜是一种高度多层的神经组织，具有多种细胞成分。随着干细胞技术的发展，人类视网膜可以在体外三维（3-D）培养中产生。然而，了解调节关键生产过程的因素以及它们如何影响发育的方式还远不清楚。氧作为参与代谢的最基本元素，是调节有机发育的关键因素。在这项研究中，我们使用人类干细胞的 3-D 培养，研究了间歇性高氧处理（40%O2）对胚胎体（EB）中神经视网膜（NR）形成和细胞行为的影响。在第 38、50 和 62 天，EB 的体积和增殖细胞的数量在 40%O2 下显著增加。此外，NR 内 PAX6+细胞的比例显著增加。只有在 40%O2 下，神经玫瑰花结才能以正确的顶底极性发育。此外，视网膜神经节细胞的生成、迁移和成熟在 40%O2 下得到增强。所有这些结果表明，40%O2 增强了 EB 中 NR 的形成，具有类似于体内状态的特征，这表明高氧状态促进了体外视网膜的发育。
