Proliferation potential of Müller glia after retinal damage varies between mouse strains.
Proliferation potential of Müller glia after retinal damage varies between mouse strains.
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DOI：
10.1371/journal.pone.0094556
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Takahashi M
中科院分区：
文献类型：
--
作者：
Suga A;Sadamoto K;Fujii M;Mandai M;Takahashi M
在鱼类、鸟类和哺乳动物中，视网膜Müler神经胶质细胞可以作为受损视网膜神经元再生的来源。然而，据报道，在哺乳动物的视网膜中，Müler胶质细胞的增殖率很低。为了解决这一问题，人们研究了生长因子和形态发生因子作为Müller神经胶质细胞增殖的强效促进剂，但限制哺乳动物视网膜Müler神经胶质细胞增殖的分子机制尚不清楚。在目前的研究中，我们发现损伤诱导的Müler胶质细胞增殖的程度在不同的小鼠品系中是不同的。光感受器细胞死亡后，小鼠细胞系129×1/SVJ(129)的增殖反应明显大于C57BL/6(B6)。用糖原合成酶激酶3(GSK3)抑制剂治疗可促进129小鼠视网膜Müler胶质细胞的增殖，但不能促进B6小鼠视网膜的增殖。因此，我们重点研究了B6和129在视网膜退行性变过程中的不同基因表达模式。Cyclin D1和Nestin的表达水平与Müller胶质细胞的增殖程度相关。对B6和129的全基因组基因表达的比较表明，损伤后视网膜中有不同的基因上调，包括免疫反应基因和染色质重塑因子。
Retinal Müller glia can serve as a source for regeneration of damaged retinal neurons in fish, birds and mammals. However, the proliferation rate of Müller glia has been reported to be low in the mammalian retina. To overcome this problem, growth factors and morphogens have been studied as potent promoters of Müller glial proliferation, but the molecular mechanisms that limit the proliferation of Müller glia in the mammalian retina remain unknown. In the present study, we found that the degree of damage-induced Müller glia proliferation varies across mouse strains. In mouse line 129×1/SvJ (129), there was a significantly larger proliferative response compared with that observed in C57BL/6 (B6) after photoreceptor cell death. Treatment with a Glycogen synthase kinase 3 (GSK3) inhibitor enhanced the proliferation of Müller glia in 129 but not in B6 mouse retinas. We therefore focused on the different gene expression patterns during retinal degeneration between B6 and 129. Expression levels of Cyclin D1 and Nestin correlated with the degree of Müller glial proliferation. A comparison of genome-wide gene expression between B6 and 129 showed that distinct sets of genes were upregulated in the retinas after damage, including immune response genes and chromatin remodeling factors.
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影响因子：
4.8
作者：
Hatakeyama, J;Kageyama, R
通讯作者：
Kageyama, R
影响因子：
3.7
作者：
Bramall, Alexa N.;Szego, Michael J.;McInnes, Roderick R.
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McInnes, Roderick R.
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作者：
CHEN, ST;GAREY, LJ;JEN, LS
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JEN, LS
影响因子：
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作者：
Das, Gaurav;Clark, Anna M.;Levine, Edward M.
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Levine, Edward M.
影响因子：
25
作者：
Fischer, AJ;Reh, TA
通讯作者：
Reh, TA