Mitogen-activated protein kinase-signaling regulates the ability of Müller glia to proliferate and protect retinal neurons against excitotoxicity.
Mitogen-activated protein kinase-signaling regulates the ability of Müller glia to proliferate and protect retinal neurons against excitotoxicity.
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DOI：
10.1002/glia.20868
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发表时间：
2009-11-01
期刊：
影响因子：
6.2
通讯作者：
Sherwood, Patrick
中科院分区：
文献类型：
--
作者：
Fischer, Andy J.;Scott, Melissa A.;Ritchey, Eric R.;Sherwood, Patrick
The purpose of this study was to investigate whether signaling through insulin, Fibroblast Growth Factor (FGF) receptors, and Mitogen-Activated Protein Kinase (MAPK) pathways protect retinal neurons against excitotoxicity and regulate the proliferation of Müller glia. We found that intraocular injections of insulin or FGF2 had variable effects upon the phosphorylation of ERK1/2, p38 MAPK and CREB, and the expression of immediate early genes, cFos and Egr1. Accumulations of pERK1/2, p38 MAPK, pCREB, cFos and Egr1 in response to insulin or FGF2 were confined to Müller glia, whereas retinal neurons did not appear to respond to growth factors. Unlike FGF2, insulin stimulated microglia-like cells to up-regulate the intermediate filament transitin and lysosomal membrane glycoprotein (LMG). The affects of insulin and FGF2 upon microglia-like cells and/or MAPK-signaling in Müller glia had profound effects upon numbers of dying neurons in response to excitotoxic damage. Although FGF2 significantly reduced numbers of dying neurons, insulin significantly increased numbers of dying neurons. In addition to neuroprotective affects, FGF2 also “primed” the Müller glia to proliferate following retinal damage, whereas insulin had no effect upon glial proliferation. Further, we found that FGF receptor isoform 1 (FGFR1) and FGFR3 are prominently expressed in the retina, whereas the insulin receptor and FGFR2 are not expressed, or are expressed at very low levels. We conclude that MAPK-signaling through FGF receptors stimulates Müller glia to become more neuroprotective and progenitor-like, whereas insulin acting on Müller and microglia-like cells through unidentified receptors had the opposite effect.
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影响因子：
25
作者：
Fischer, AJ;Reh, TA
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0807453105
发表时间：
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影响因子：
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