EARLY REMODELING IN AN INDUCIBLE ANIMAL MODEL OF RETINAL DEGENERATION
EARLY REMODELING IN AN INDUCIBLE ANIMAL MODEL OF RETINAL DEGENERATION
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DOI：
10.1016/j.neuroscience.2009.02.056
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发表时间：
2009-05-05
期刊：
影响因子：
3.3
通讯作者：
Dhingra, N. K.
中科院分区：
文献类型：
--
作者：
Nagar, S.;Krishnamoorthy, V.;Dhingra, N. K.
在人类和几种遗传动物模型中，光感受器变性之后是二级视网膜神经元的显著形态学变化。然而，目前尚不清楚是否发生类似的变化时，感光细胞变性是诱导非遗传性，提出了一个问题，这些变化是否是一个独立的变性的原因deafferentation的一般效果。我们通过用N-甲基-N-亚硝基脲（MNU）诱导选择性光感受器变性并使用免疫细胞化学和离子电渗标记研究其对小鼠视网膜内层神经元的影响长达3个月来解决这一问题。为了开发光感受器变性和视网膜重塑的客观测量，我们使用免疫印迹分析测量了几种视网膜蛋白，并在视觉悬崖测试中量化了动物的总视觉能力。MNU诱导的视杆细胞和视锥细胞的进行性变性与视网膜中突触后密度95蛋白水平的下降以及动物视觉性能的恶化有关。Muller神经胶质细胞表现出对胶质细胞酸性蛋白的增强的反应性，如通过免疫细胞化学所证明的，这也反映在通过免疫印迹所证明的蛋白质水平增加中。水平细胞和杆双极细胞逐渐失去了树突状突起，这与钙结合蛋白和蛋白激酶C α水平分别略有下降。水平的细胞轴突，非磷酸化神经丝的免疫反应，显示发芽到内核层。神经节细胞和他们的突触输入，探测免疫定位β-III-微管蛋白，神经丝，巴松管和突触素，似乎不受影响。这些结果表明，MNU诱导的光感受器变性导致视网膜重塑类似于在遗传模型中观察到的，表明重塑不依赖于光感受器变性的病因病理学。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Photoreceptor degeneration is followed by significant morphological changes in the second-order retinal neurons in humans and in several genetic animal models. However, it is not clear whether similar changes occur when photoreceptor degeneration is induced nongenetically, raising the question whether these changes are a general effect of deafferentation independent of the cause of degeneration. We addressed this by inducing selective photoreceptor degeneration with N-methyl-N-nitrosourea (MNU) and studying its effects on inner retinal neurons in a mouse for up to 3 months, using immunocytochemistry and iontophoretic labeling. To develop objective measures of photoreceptor degeneration and of retinal remodeling, we measured several retinal proteins using immunoblot analysis, and quantified gross visual ability of the animal in a visual cliff test. The MNU-induced progressive degeneration of rods and cones was associated with declining levels of postsynaptic density 95 protein in the retina, and with deteriorating visual performance of the animal. Muller glial cells showed enhanced reactivity for glial fibrillary acidic protein as demonstrated by immunocytochemistry, which also reflected in increased levels of the protein as demonstrated by immunoblotting. Horizontal cells and rod bipolar cells progressively lost their dendritic processes, which correlated with a slight decline in the levels of calbindin and protein kinase C alpha respectively. Horizontal cell axons, immunoreactive for nonphosphorylated neurofilaments, showed sprouting into the inner nuclear layer. Ganglion cells and their synaptic inputs, probed by immunolocalizing beta-III-tubulin, neurofilaments, bassoon and synaptophysin, appeared to be unaffected. These results demonstrate that MNU-induced photoreceptor degeneration leads to retinal remodeling similar to that observed in genetic models, suggesting that the remodeling does not depend on the etiopathology that underlies photoreceptor degeneration. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.