Instituto de Neurociencias (CSIC-UMH), Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández, Campus San Juan, Av. Ramón y Cajal s/n, Alicante, 03550, Spain.
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Prog Retin Eye Res. 2019 Jan;68:110-123. doi: 10.1016/j.preteyeres.2018.09.001. Epub 2018 Sep 8.
Numerous degenerative diseases affecting visual function, including glaucoma and retinitis pigmentosa, are produced by the loss of different types of retinal cells. Cell replacement therapy has emerged as a promising strategy for treating these and other retinal diseases. The retinal margin or ciliary body (CB) of mammals has been proposed as a potential source of cells to be used in degenerative conditions affecting the retina because it has been reported it might hold neurogenic potential beyond embryonic development. However, many aspects of the origin and biology of the CB are unknown and more recent experiments have challenged the capacity of CB cells to generate different types of retinal neurons. Here we review the most recent findings about the development of the marginal zone of the retina in different vertebrates and some of the mechanisms underlying the proliferative and neurogenic capacity of this fascinating region of the vertebrates eye. In addition, we performed experiments to isolate CB cells from the mouse retina, generated neurospheres and observed that they can be expanded with a proliferative ratio similar to neural stem cells. When induced to differentiate, cells derived from the CB neurospheres start to express early neural markers but, unlike embryonic stem cells, they are not able to fully differentiate in vitro or generate retinal organoids. Together with previous reports on the neurogenic capacity of CB cells, also reviewed here, our results contribute to the current knowledge about the potentiality of this peripheral region of the eye as a therapeutic source of functional retinal neurons in degenerative diseases.
许多影响视觉功能的退行性疾病，包括青光眼和色素性视网膜炎，都是由不同类型的视网膜细胞丧失引起的。细胞替代疗法已成为治疗这些和其他视网膜疾病的一种有前途的策略。哺乳动物的视网膜边缘或睫状体（CB）已被提议作为用于影响视网膜的退行性疾病的细胞来源，因为据报道，它可能具有超越胚胎发育的神经发生潜力。然而，CB 的起源和生物学的许多方面尚不清楚，最近的实验也挑战了 CB 细胞产生不同类型的视网膜神经元的能力。在这里，我们回顾了不同脊椎动物视网膜边缘区发育的最新发现，以及该脊椎动物眼睛这一迷人区域增殖和神经发生能力的一些潜在机制。此外，我们还进行了从鼠视网膜分离 CB 细胞、生成神经球并观察它们的实验，结果表明它们可以以类似于神经干细胞的增殖比例进行扩增。当诱导分化时，源自 CB 神经球的细胞开始表达早期神经标记物，但与胚胎干细胞不同，它们不能在体外完全分化或生成视网膜类器官。结合这里也回顾的关于 CB 细胞神经发生能力的先前报告，我们的结果有助于了解眼睛这个外围区域作为退行性疾病功能性视网膜神经元治疗来源的潜力。
