Nickerson P E B, Da Silva N, Myers T, Stevens K, Clarke D B
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Canada.
Brain Res. 2008 Sep 16;1230:1-12. doi: 10.1016/j.brainres.2008.03.095. Epub 2008 Jul 8.
The Müller radial glial cell is the principal support cell of the adult mammalian retina. Recent reports suggest that these cells retain the capacity to proliferate, express phenotypes reminiscent of retinal progenitor cells (RPC) and generate neuron-like progeny. We isolated rodent Müller cells and generated cultures that could be passaged under conditions used in neural stem/progenitor cell colonies. We demonstrate that during the early period of primary culture, Müller glia proliferate into sphere colonies and express a select regimen of phenotypes normally seen in RPCs. This effect correlates temporally with the loss of retinal neurons post-dissection. When chronically maintained in vitro, Müller cells can be repeatedly passaged, and up-regulate early RPC phenotypes that are suggestive of cellular de-differentiation. Furthermore, exposure of Müller glial cultures to differentiating conditions containing growth factors stimulates Müller glia to up-regulate phenotypes associated with retinal neurons. These data provide further evidence that isolated, adult Müller glia retain functional and phenotypic features of RPCs.
米勒放射状胶质细胞是成年哺乳动物视网膜的主要支持细胞。最近的报告表明,这些细胞保留了增殖能力,表达出类似于视网膜祖细胞(RPC)的表型,并产生神经元样后代。我们分离了啮齿动物的米勒细胞,并建立了可以在神经干细胞/祖细胞集落培养条件下传代的培养物。我们证明,在原代培养的早期,米勒胶质细胞增殖形成球状体集落,并表达RPC中通常可见的特定表型组合。这种效应在时间上与解剖后视网膜神经元的丧失相关。当在体外长期培养时,米勒细胞可以反复传代,并上调提示细胞去分化的早期RPC表型。此外,将米勒胶质细胞培养物暴露于含有生长因子的分化条件下,会刺激米勒胶质细胞上调与视网膜神经元相关的表型。这些数据进一步证明,分离的成年米勒胶质细胞保留了RPC的功能和表型特征。