Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG study
Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG study
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DOI：
10.1002/cne.21144
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发表时间：
2007-01-10
影响因子：
2.5
通讯作者：
Strettoi, Enrica
中科院分区：
文献类型：
--
作者：
Gargini, Claudia;Terzibasi, Eva;Strettoi, Enrica
视网膜变性10 （rd10）小鼠是常染色体隐性视网膜色素变性（RP）的模型，由Chang等人于2002年发现（Vision Res. 42:517-525）。这些小鼠携带杆状蛋白磷酸二酯酶（PDE）基因的自发突变，导致杆状蛋白在P18左右开始变性。之后，视锥细胞也会丢失。由于光感受器退化与视网膜发育不重叠，并且出生后大约一个月的光反应可以被记录下来，rd10小鼠比众所周知的rd1突变体更接近典型的人类RP。本研究的目的是全面分析rd10小鼠视网膜在最大光感受器变性时期的形态和功能，从而为利用这种新模型研究RP提供有用的数据。采用定量免疫细胞化学和共聚焦显微镜技术分析不同年龄rd10小鼠视网膜细胞形态和存活情况；我们还用视网膜电图（ERG）研究了P18和P30之间的视网膜功能。我们发现光感受器死亡（在P25左右达到峰值）伴随着双极细胞和水平细胞的树突缩回，并最终发生继发性变性。早在P18（在任何明显的内神经元形态学改变之前），ERG就显示了内视网膜的生理变化，但与双极细胞的能带扩增减少一致。因此，rd10视网膜的变化与之前在rd1突变体中发现的变化非常相似。然而，视网膜结构和功能整体较慢的衰退预示着rd10小鼠可能成为治疗方法的优秀模型。
Retinal degeneration 10 (rd10) mice are a model of autosomal recessive retinitis pigmentosa (RP), identified by Chang et al. in 2002 (Vision Res. 42:517-525). These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE) gene, leading to a rod degeneration that starts around P18. Later, cones are also lost. Because photoreceptor degeneration does not overlap with retinal development, and light responses can be recorded for about a month after birth, rd10 mice mimic typical human RP more closely than the well-known rd1 mutants. The aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the period of maximum photoreceptor degeneration, thus contributing useful data for exploiting this novel model to study RP. We analyzed the morphology and survival of retinal cells in rd10 mice of various ages with quantitative immunocytochemistry and confocal microscopy; we also studied retinal function with the electroretinogram (ERG), recorded between P18 and P30. We found that photoreceptor death (peaking around P25) is accompanied and followed by dendritic retraction in bipolar and horizontal cells, which eventually undergo secondary degeneration. ERG reveals alterations in the physiology of the inner retina as early as P18 (before any obvious morphological change of inner neurons) and yet consistently with a reduced band amplification by bipolar cells. Thus, changes in the rd10 retina are very similar to what was previously found in rd1 mutants. However, an overall slower decay of retinal structure and function predicts that rd10 mice might become excellent models for rescue approaches.