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.
ABSTRACT Recent studies have demonstrated that insulin can have profound affects on 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 that these cells can 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 express 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 nonastrocytic 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 upregulating transitin. In addition, IGF1 stimulated microglia to become reactive and upregulate 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 the 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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ABSTRACT: Oligodendrocytes are derived from glial precursors that arise from the ventral neural tube early in development. In the developing chicken CNS, oligodendrocyte progenitors selectively express Nkx2.2 homeodomain transcription factor, raising the possibility that Nkx2.2 may directly regulate oligogliogenesis. In this study, we have examined Nkx2.2 expression in rodent glial precursors and studied the effect of a loss of Nkx2.2 on oligodendrocyte and astrocyte differentiation. We show that Nkx2.2 is also expressed in mammalian oligodendrocyte progenitors and that the differentiation of MBP-positive and PLP-DM20-positive oligodendrocytes is dramatically retarded in Nkx2.2-null mutants along the entire rostrocaudal axis. In contrast, no effect is seen on astrocytic differentiation. Interestingly, absence of Nkx2.2 expression leads to a ventral expansion of the Olig1/Olig2 expression in neuroepithelial cells into the Nkx2.2 domain and a consequent increase in the production of Olig1/Olig2-positive and platelet-derived growth factor receptor alpha-positive oligodendrocyte progenitors. These results strongly suggest that Nkx2.2 regulates the differentiation and/or maturation, but not the initial specification, of oligodendrocyte progenitors. Consistent with this suggestion, overproduction of Nkx2.2 protein in fibroblast cells can induce gene expression from the proteolipid protein promoter.Development 08/2001; 128(14):2723-33. · 6.60 Impact Factor
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ABSTRACT: Programmed cell death is an essential process for proper neural development. Cell death, with its similar regulatory and executory mechanisms, also contributes to the origin or progression of many or even all neurodegenerative diseases. An understanding of the mechanisms that regulate cell death during neural development may provide new targets and tools to prevent neurodegeneration. Many studies that have focused mainly on insulin-like growth factor-I (IGF-I), have shown that insulin-related growth factors are widely expressed in the developing and adult nervous system, and positively modulate a number of processes during neural development, as well as in adult neuronal and glial physiology. These factors also show neuroprotective effects following neural damage. Although some specific actions have been demonstrated to be anti-apoptotic, we propose that a broad neuroprotective role is the foundation for many of the observed functions of the insulin-related growth factors, whose therapeutical potential for nervous system disorders may be greater than currently accepted.Molecular Neurobiology 09/2003; 28(1):23-50. · 5.74 Impact Factor