Retinal functional alterations in mice lacking intermediate filament proteins glial fibrillary acidic protein and vimentin
Retinal functional alterations in mice lacking intermediate filament proteins glial fibrillary acidic protein and vimentin
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DOI：
10.1096/fj.15-272963
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发表时间：
2015-08
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通讯作者：
K. Wunderlich;N. Tanimoto;A. Grosche;E. Zrenner;M. Pekny;A. Reichenbach;M. Seeliger;T. Pannicke;Maria-Thereza R. Perez
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作者：
K. Wunderlich;N. Tanimoto;A. Grosche;E. Zrenner;M. Pekny;A. Reichenbach;M. Seeliger;T. Pannicke;Maria-Thereza R. Perez
波形蛋白(Vim)和胶质纤维酸性蛋白(GFAP)是星形胶质细胞中间丝(IF)(或纳米丝)系统的重要组成部分。我们进行了全场视网膜电图(ERG)记录，发现未损伤的GFAP-/-Vim-/-小鼠的光感受器反应(a波)正常，b波幅度增加。此外，我们还发现在GFAP-/-Vim-/-小鼠视网膜中KIR(内向整流钾)通道蛋白表达减少，并且KIR介导的电流幅度在这些小鼠的Müler神经胶质细胞中较低。研究表明，IF系统还参与了视网膜对损伤的反应，在实验性视网膜脱离后，IF缺陷小鼠的Müler细胞反应性减弱，光感受器细胞丢失减少。我们研究了在视网膜缺血-再灌注模型中，IF蛋白的缺乏是否会影响细胞的存活。我们发现，尽管这两种基因都会导致细胞丢失，但IF缺陷小鼠视网膜内存活的细胞数量较少。因此，我们的研究结果表明，不能产生GFAP和Vim影响正常的视网膜生理，IF缺乏对视网膜细胞存活的影响因潜在的病理条件而异。-Wunderlich，K.A.，TAnimoto，N.，Grosche，A.，Zrenner，E.，Pekny，M.，Reichenbach，A.，Sealier，M.W.，Pannicke，T.，Perez，M.-T.缺乏中间丝蛋白、胶质纤维酸性蛋白和波形蛋白的小鼠视网膜功能改变。FASE B J.29,4815-4828(2015)。Www.fasebj.org
Vimentin (Vim) and glial fibrillary acidic protein (GFAP) are important components of the intermediate filament (IF) (or nanofilament) system of astroglial cells. We conducted full‐field electroretinogram (ERG) recordings and found that whereas photoreceptor responses (a‐wave) were normal in uninjured GFAP–/– Vim–/– mice, b‐wave amplitudes were increased. Moreover, we found that Kir (inward rectifier K+) channel protein expression was reduced in the retinas of GFAP–/– Vim–/– mice and that Kir‐mediated current amplitudes were lower in Müller glial cells isolated from these mice. Studies have shown that the IF system, in addition, is involved in the retinal response to injury and that attenuated Müller cell reactivity and reduced photoreceptor cell loss are observed in IF‐deficient mice after experimental retinal detachment. We investigated whether the lack of IF proteins would affect cell survival in a retinal ischemia‐reperfusion model. We found that although cell loss was induced in both genotypes, the number of surviving cells in the inner retina was lower in IF‐deficient mice. Our findings thus show that the inability to produce GFAP and Vim affects normal retinal physiology and that the effect of IF deficiency on retinal cell survival differs, depending on the underlying pathologic condition.—Wunderlich, K. A., Tanimoto, N., Grosche, A., Zrenner, E., Pekny, M., Reichenbach, A., Seeliger, M. W., Pannicke, T., Perez, M.‐T. Retinal functional alterations in mice lacking intermediate filament proteins glial fibrillary acidic protein and vimentin. FASEB J. 29, 4815–4828 (2015). www.fasebj.org