Spatiotemporal pattern of rod degeneration in the S334ter-line-3 rat model of retinitis pigmentosa.
Spatiotemporal pattern of rod degeneration in the S334ter-line-3 rat model of retinitis pigmentosa.
复制标题
S334ter-line-3 大鼠色素性视网膜炎模型中视杆细胞退化的时空模式。
DOI：
10.1007/s00441-012-1522-5
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发表时间：
2013
影响因子：
3.6
通讯作者：
Grzywacz,NorbertoM
中科院分区：
文献类型：
--
作者：
Zhu,ColleenL;Ji,Yerina;Lee,Eun-Jin;Grzywacz,NorbertoM
我们最近描述了色素性视网膜炎（RP）中幸存的视锥细胞和mller -胶质细胞过程重塑，并表明视杆变性触发视锥细胞马赛克重组为有序的环阵列。在这些环内，重塑的<s:1>勒神经胶质细胞处理包膜锥体。在这里，我们报道了健康视杆细胞的时空模式，它们与死亡视杆细胞的关系，以及视杆细胞死亡刺激视锥细胞空间分布模式和<s:1>勒-胶质细胞过程改变的方式，这是一种表达导致RP的视紫红质突变的转基因模型。采用免疫细胞化学方法，用细胞类型特异性标记物标记大鼠视网膜各发育阶段的视杆细胞、视锥细胞、小胶质细胞和突触细胞的空间格局。TUNEL染色观察死亡细胞的空间格局。大约在出生后第10天左右，S334ter杆镶嵌开始出现小孔。这些细胞死亡热点的大小逐渐增加，留下更大的无杆孔。这些孔洞暂时被活跃的小胶质细胞占据，然后被重塑的<s:1>勒细胞突所取代。我们的数据表明，在视网膜退行性变的早期，杆状细胞死亡的热点在杆状细胞镶嵌中产生孔洞，由此产生的图案引发了视锥细胞和神经胶质细胞空间分布模式的改变。
We have recently described the surviving cones and Müller-glia process remodeling in retinitis pigmentosa (RP) and shown that rod degeneration triggers the reorganization of the cone mosaic into an orderly array of rings. Within these rings, remodeled Müller-glia processes envelope cones. Here, we report the spatiotemporal pattern of healthy rods, their relationship with dying rods and the way that rod death stimulates the modification of cone spatial-distribution patterns and Müller-glia processes in the S334ter-line-3 rat, a transgenic model expressing a rhodopsin mutation that causes RP. The spatial patterns of rods, cones, microglial and Müller cells were labeled by immunocytochemistry with cell-type-specific markers at various stages of deveopment in rat whole-mount retinas. Spatial patterns of dying cells were examined by TUNEL staining. The S334ter rod mosaic began to develop small holes around postnatal day 10. These hot-spots of cell death progressively increased in size, leaving larger rod-less holes behind. The holes were temporarily occupied by active microglial cells, before being replaced by remodeled Müller-cell processes. Our data suggest that the hot spots of rod death create holes in the rod mosaic early in retinal degeneration and that the resulting pattern triggers the modification of the spatial-distribution patterns of cones and glia cells.