Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects.
Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects.
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DOI：
10.1186/s12974-014-0186-3
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发表时间：
2014-10-29
影响因子：
9.3
通讯作者：
Cuenca N
中科院分区：
文献类型：
--
作者：
Noailles A;Fernández-Sánchez L;Lax P;Cuenca N
色素性视网膜炎是一组异质性遗传性神经退行性视网膜疾病，以进行性周边视力丧失和夜视困难为特征，继而导致中枢性视力障碍。慢性小胶质细胞激活与包括视网膜色素变性在内的多种神经退行性疾病有关。本研究的目的是定量检测视网膜色素变性动物模型P23H大鼠视网膜小胶质细胞的活性，并评价神经保护化合物牛磺酸脱氧胆酸(TUDCA)的治疗作用。在本研究中，纯合子P23H系3和SD大鼠从20日龄到4月龄每周注射TUDCA(500 mg/kg，ip)或赋形剂(生理盐水)。用免疫组织化学方法检测小胶质细胞的特异性标志物(抗CD11b、抗Iba1和抗MHC-II)。对小胶质细胞形态进行分析，并对视网膜小胶质细胞数量进行定量。SD大鼠视网膜小胶质细胞呈规则的马赛克状排列，均匀分布于神经丛细胞层和神经节细胞层。P23H大鼠视网膜各层小胶质细胞较对照SD大鼠增多，仍保持规则的镶嵌分布。此外，在P23H大鼠的视网膜，甚至在视网膜下间隙，也观察到大量的变形体CD11b阳性细胞。经TUDCA处理的P23H动物视网膜各层小胶质细胞数量减少，视网膜下间隙无小胶质细胞。这些结果报告了新的TUDCA抗炎作用，对包括视网膜色素变性在内的神经退行性疾病具有潜在的治疗意义。
Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigmentosa. The objective of this study was to quantify microglia activation in the retina of P23H rats, an animal model of retinitis pigmentosa, and to evaluate the therapeutic effects of TUDCA (tauroursodeoxycholic acid), which has been described as a neuroprotective compound. For this study, homozygous P23H line 3 and Sprague-Dawley (SD) rats were injected weekly with TUDCA (500 mg/kg, ip) or vehicle (saline) from 20 days to 4 months old. Vertical retinal sections and whole-mount retinas were immunostained for specific markers of microglial cells (anti-CD11b, anti-Iba1 and anti-MHC-II). Microglial cell morphology was analyzed and the number of retinal microglial was quantified. Microglial cells in the SD rat retinas were arranged in regular mosaics homogenously distributed within the plexiform and ganglion cell layers. In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution. In addition, a large number of amoeboid CD11b-positive cells were observed in the P23H rat retina, even in the subretinal space. Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space. These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.
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DOI：
10.4172/2155-9899
发表时间：
2013
期刊：
Journal of clinical & cellular immunology
影响因子：
--
作者：
Abcouwer SF
通讯作者：
Abcouwer SF
影响因子：
13.5
作者：
Harry, G. Jean
通讯作者：
Harry, G. Jean
影响因子：
3.3
作者：
Hayashi, Y.;Tomimatsu, Y.;Nakanishi, H.
通讯作者：
Nakanishi, H.
影响因子：
3.3
作者：
Gaspar, J. M.;Martins, A.;Santiago, A. R.
通讯作者：
Santiago, A. R.
影响因子：
2.5
作者：
Bosco, Alejandra;Steele, Michael R.;Vetter, Monica L.
通讯作者：
Vetter, Monica L.