Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.
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DOI:
10.1002/cne.22322
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发表时间:
2010-06-01
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Sherry DM
Sherry DM
中科院分区:
其他
文献类型:
--
作者:
Phillips MJ;Otteson DC;Sherry DM

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Pde 6 brd 10(rd 10)小鼠具有中等的感光细胞变性率,可作为人常染色体隐性视网膜色素变性(RP)的有价值模型。我们评估了从出生后第30天(P30)到出生后第9.5个月(PNM9.5)的不同退化阶段的Pde 6 brd 10(rd 10)小鼠视网膜中的第二和第三级视网膜细胞及其突触末梢的神经元重塑的进展,使用免疫标记法对众所周知的细胞和突触特异性标记物进行标记。光感受器丧失后,从视网膜外层到内层逐渐发生变化。水平细胞和杆和锥双极细胞进行形态重塑,包括树突的损失,细胞体迁移,和发芽的异位过程。神经胶质增生,其特征是Müller细胞体移位到视网膜外层,其突起增厚,在P30时明显,并随着变性的进展而变得更加明显。视杆细胞变性后,VGluT 1在视网膜外层的持续表达与附近二级神经元的存活和突触蛋白的表达相关。PNM 3.5时,视杆双极细胞终末逐渐缩小,异位双极细胞突起延伸至内核层和神经节细胞层。推测的异位常规突触,可能来自无长突细胞,存在于内核层PNM9.5。尽管有这些变化,双极和无长突细胞的层状组织和ON-OFF组织的内网状层在很大程度上保留。存活的锥细胞和双极细胞终端继续表达突触功能所需的适当的细胞特异性突触前蛋白质高达PNM9.5。
The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6brd10 (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5.
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