Ren J C, LaVail M M, Peachey N S
Program in Neuroscience, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
Exp Eye Res. 2000 Apr;70(4):467-73. doi: 10.1006/exer.1999.0804.
The nervous (nr) mutation induces a progressive and severe degeneration of cerebellar Purkinje cells and retinal photoreceptors that is virtually complete within the first few months of life. Previous studies of the retina in nervous (nr/nr) mice have focused primarily on the structural abnormalities seen at the level of the photoreceptor cell bodies and outer segments. Here, we have carried out a series of functional studies of the visual pathway in nervous mice and have quantified the status of the inner retinal cell and plexiform layers. Affected animals were obtained by mating nr/+ heterozygotes and screening the offspring for the ataxia characteristic of nervous animals; phenotypically normal littermates (i.e. nr/+ or +/+) were used as controls. As described previously, there is a substantial loss of photoreceptors cells in the nervous retina and a marked shortening of the inner and outer segments. These changes are accompanied by a more modest decline in the thickness of the inner plexiform and inner nuclear layers. These anatomic abnormalities were accompanied by reproducible changes in visual function, as measured with the electroretinogram (ERG) and visual evoked potential (VEP). The dark-adapted ERGs of nervous and control mice had similar waveforms, although the nervous responses were substantially smaller in amplitude. The reductions in the amplitude of the ERG a-wave corresponded to the loss of photoreceptor cells and shortened outer segments seen histologically. Nevertheless, the kinetics of the leading edge of the a-wave did not differ between nervous and control mice, indicating that the rod outer segments of nervous mice continue to respond to light in a normal fashion. The amplitudes of cone ERGs were also reduced in nervous mice, although the extent of this reduction in any given animal was always less than that for rod-mediated ERG components. Overall, this result is consistent with cone involvement occurring only as a secondary effect of rod photoreceptor degeneration. The peak latencies of VEPs of nervous mice were slower than those of control littermates. These functional abnormalities correspond well to the structural changes induced by the nervous mutation, which does not appear to prevent visual signals from being transmitted centrally, beyond the limitations imposed by the degenerative process.
神经（nr）突变会导致小脑浦肯野细胞和视网膜光感受器进行性严重退化，在出生后的头几个月内几乎完全退化。先前对神经（nr/nr）小鼠视网膜的研究主要集中在光感受器细胞体和外段水平上观察到的结构异常。在这里，我们对神经小鼠的视觉通路进行了一系列功能研究，并对内视网膜细胞和神经纤维层的状态进行了量化。通过将nr/+杂合子交配并筛选后代中神经动物特有的共济失调来获得受影响的动物；表型正常的同窝小鼠（即nr/+或+/+）用作对照。如先前所述，神经视网膜中的光感受器细胞大量丧失，内段和外段明显缩短。这些变化伴随着内神经纤维层和内核层厚度的更适度下降。这些解剖学异常伴随着视觉功能的可重复变化，通过视网膜电图（ERG）和视觉诱发电位（VEP）测量。神经小鼠和对照小鼠的暗适应ERG具有相似的波形，尽管神经小鼠的反应幅度明显较小。ERG a波幅度的降低与组织学上观察到的光感受器细胞丧失和外段缩短相对应。然而，神经小鼠和对照小鼠a波前沿的动力学没有差异，表明神经小鼠的视杆外段继续以正常方式对光作出反应。神经小鼠的视锥ERG幅度也降低了，尽管在任何给定动物中这种降低的程度总是小于视杆介导的ERG成分。总体而言，这一结果与视锥细胞仅作为视杆光感受器退化的继发效应参与其中是一致的。神经小鼠VEP的峰值潜伏期比对照同窝小鼠的要慢。这些功能异常与神经突变引起的结构变化非常吻合，神经突变似乎并没有阻止视觉信号在中枢的传递，只是超出了退化过程所带来的限制。
