A novel type of glial cell in the retina is stimulated by insulin-like growth factor 1 and may exacerbate damage to neurons and Müller glia.

A novel type of glial cell in the retina is stimulated by insulin-like growth factor 1 and may exacerbate damage to neurons and Müller glia.
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DOI:
10.1002/glia.20950
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发表时间:
2010-04-15
期刊:
影响因子:
6.2
通讯作者:
Sherwood, Patrick
Sherwood, Patrick
中科院分区:
医学1区
文献类型:
--
作者:
Fischer, Andy J.;Scott, Melissa A.;Zelinka, Christopher;Sherwood, Patrick

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最近的研究表明,胰岛素可以对视网膜内神经元的存活产生深远的影响。这项研究的目的是确定胰岛素样生长因子1(IGF1)如何影响视网膜细胞,特别是胶质细胞。我们在鸟类视网膜中发现了一种新类型的神经胶质细胞,并为这些细胞对急性损伤和IGF1做出反应提供了证据。在正常视网膜中,我们发现了一种独特的细胞类型,分布于神经节细胞和内丛状层,表达Sox2、Sox9、Nkx2.2、vientin和哺乳动物Nestin的鸟类同源物Transftin。这些胶质细胞具有独特的免疫组织化学特征、形态和分布,与其他已知类型的视网膜胶质细胞不同,包括小胶质细胞、少突胶质细胞、星形胶质细胞和Muller胶质细胞。我们称这些细胞为非星形细胞视网膜内胶质样细胞(NIRG细胞)。我们发现,NIRG细胞可能表达IGF1受体,并通过增殖、向视网膜远端迁移和上调转移蛋白来对IGF1作出反应。此外,IGF1刺激小胶质细胞发生反应,上调溶酶体膜糖蛋白和CD45的表达。在IGF1刺激的小胶质细胞和NIRG细胞中,由于兴奋性毒性损伤,细胞死亡水平增加,视网膜上出现大量局灶性分离。细胞死亡在脱离区明显,同时伴有Müler胶质细胞的明显丧失和NIRG细胞的聚集。我们认为,NIRG细胞是一种对IGF1敏感的新型视网膜胶质细胞,其活性可能影响神经元和Müler神经胶质细胞的存活。
Recent studies have demonstrated that insulin can have profound affects upon the survival of neurons within the retina. The purpose of this study was to determine how insulin-like growth factor 1 (IGF1) influences retinal cells; in particular the glial cells. We identify a novel type of glial cell in the avian retina and provide evidence these cells respond to acute damage and IGF1. In normal retinas, we found a distinct cell-type, scattered across the ganglion cell and inner plexiform layers, that expressed Sox2, Sox9, Nkx2.2, vimentin and transitin, the avian homologue of mammalian nestin. These glial cells have a unique immunohistochemical profile, morphology and distribution that are distinct among other known types of retinal glia, including microglia, oligodendrocytes, astrocytes and Muller glia. We termed these cells Non-astrocytic Inner Retinal Glia-like (NIRG) cells. We found that the NIRG cells may express the IGF1 receptor and respond to IGF1 by proliferating, migrating distally into the retina, and up-regulating transitin. In addition, IGF1 stimulated microglia to become reactive and up-regulate lysosomal membrane glycoprotein and CD45. With microglia and NIRG cells stimulated by IGF1 there were elevated levels of cell death and numerous focal detachments across the retina in response to excitotoxic damage. Cell death was prominent within areas of detachment coinciding with a stark loss of Müller glia and accumulation of NIRG cells. We conclude that NIRG cells are a novel type of retinal glia that is sensitive to IGF1 and whose activity may impact the survival of neurons and Müller glia.
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