Regressive and reactive changes in the connectivity patterns of rod and cone pathways of P23H transgenic rat retina
Regressive and reactive changes in the connectivity patterns of rod and cone pathways of P23H transgenic rat retina
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DOI：
10.1016/j.neuroscience.2004.04.042
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Lund, RD
中科院分区：
文献类型：
--
作者：
Cuenca, N;Pinilla, I;Lund, RD
我们利用P23H系1纯合子白化大鼠研究了进行性光感受器变性如何影响杆状体和锥体接力通路。我们通过免疫染色切片和视网膜电图（ERG）记录的共聚焦显微镜检查了不同阶段的P23H视网膜变性。到21日龄时，P23H大鼠视网膜中已经有大量的杆状细胞丢失，杆状双极树突减少，代谢性谷氨酸受体6 （mGluR6）和杆状细胞相关巴松管染色减少。锥体通路相对不受影响。到第150天，当视网膜的大部分都没有视杆细胞时，一些视杆双极细胞仍然存在，视杆和视锥双极细胞的树突形成了与视锥细胞和水平细胞过程相关的突触复合体。这些复合物包括mGluR6的病灶和巴松管染色；它们在270日龄时进一步发育。从21天开始，在变性过程中，双极轴突终末萎缩，内视网膜经历进一步的变化，包括All - amacrine细胞数量减少和紊乱，内丛状层变薄。第23天的视网膜电图（ERG）结果显示，a波振幅、杆状和锥状相关的b波（使用双闪模式）以及振荡电位（OPs）的振幅都有所下降。到38天，杆状体的暗位a波响应和OPs都消失了。b波振幅下降到150天，此时它们纯粹是锥驱动的，并在250天内保持稳定。结果表明，在P23H大鼠光感受器丧失过程中，存在进行性退行性改变，特别是在杆接力通路中，这些变化反映在ERG反应模式的变化上。随后的反应性变化包括锥体末端和与杆状和锥体双极树突相关的神经递质受体的凝聚以及水平细胞过程，这表明在这一阶段，通过视网膜的感觉信息传递可能会发生复杂的变化。(c) 2004 ibro。Elsevier Ltd.出版。版权所有。
We have used the P23H line 1 homozygous albino rat to study how progressive photoreceptor degeneration affects rod and cone relay pathways. We examined P23H retinas at different stages of degeneration by confocal microscopy of immunostained sections and electroretinogram (ERG) recordings.By 21 days of age in the P23H rat retina, there is already substantial loss of rods and reduction in rod bipolar dendrites along with reduction of metabotropic glutamate receptor 6 (mGluR6) and rod-associated bassoon staining. The cone pathway is relatively unaffected. By 150 days, when rods are absent from much of the retina, some rod bipolars remain and dendrites of rod and cone bipolar cells form synaptic complexes associated with cones and horizontal cell processes. These complexes include foci of mGluR6 and bassoon staining; they develop further by 270 days of age. Over the course of degeneration, beginning at 21 days, bipolar axon terminals atrophy and the inner retina undergoes further changes including a reduced and disorganized All amacrine cell population and thinning of the inner plexiform layer. Electroretinogram (ERG) results at 23 days show reductions in a-wave amplitude, in rod and cone-associated b-waves (using a double flash paradigm) and in the amplitude of oscillatory potentials (OPs). By 38 days, rod scotopic a-wave responses and OPs are lost. B-wave amplitudes decline until 150 days, at which point they are purely cone-driven and remain stable up to 250 days.The results show that during the course of photoreceptor loss in the P23H rat, there are progressive degenerative changes, particularly in the rod relay pathway, and these are reflected in the changing ERG response patterns. Later reactive changes involving condensation of cone terminals and neurotransmitter receptors associated with rod and cone bipolar dendrites and with horizontal cell processes suggest that at this stage, there are likely to be complex changes in the relay of sensory information through the retina. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.