Differential loss and preservation of glutamate receptor function in bipolar cells in the rd10 mouse model of retinitis pigmentosa.
Differential loss and preservation of glutamate receptor function in bipolar cells in the rd10 mouse model of retinitis pigmentosa.
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DOI：
10.1111/j.1460-9568.2009.06728.x
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Taylor WR
中科院分区：
文献类型：
--
作者：
Puthussery T;Gayet-Primo J;Pandey S;Duvoisin RM;Taylor WR
光感受器的退化可以触发二级神经元的形态变化，然而，这种变化的功能含义还不是很清楚。我们进行了一项纵向研究，使用全细胞膜片钳、免疫组织化学和电子显微镜来研究RD10小鼠双极细胞的生理和解剖变化--常染色体隐性视网膜色素变性模型。视杆双极细胞(RBC)的mGluR6诱导电流随视杆感光细胞退行性变而逐渐改变。反应幅度和动力学在出生后第20天就有明显变化，到出生后45d，反应幅度下降了91%，然后保持相对稳定，直到6个月。这些功能改变与视杆感受器的缺失和mGluR6受体的表达有关。此外，我们还发现，在疾病进展过程中，视杆双极细胞与视锥细胞发生了短暂的异位连接。在P45，锥体上双极细胞比杆状双极细胞保持mGluR6反应的时间更长，但大约6个月后，这些细胞也强烈下调mGluR6的表达。我们认为，在锥体双极细胞中mGluR6反应的相对寿命是由于锥体丢失较慢所致。相比之下，锥体外双极细胞中的离子型谷氨酸受体的表达和功能在6个月后保持正常，尽管锥体突触输入丢失。因此，谷氨酸受体的表达在双极细胞中受到不同的调节，代谢性受体完全依赖于突触输入。这些发现定义了双极细胞可能接受光感受器修复或替换的时间窗口。
Photoreceptor degenerations can trigger morphological alterations in second-order neurons, however, the functional implications of such changes are not well known. We conducted a longitudinal study, using whole-cell patch-clamp, immunohistochemistry and electron microscopy to correlate physiological with anatomical changes in bipolar cells of the rd10 mouse - a model of autosomal recessive retinitis pigmentosa. Rod bipolar cells (RBCs) showed progressive changes in mGluR6-induced currents with advancing rod photoreceptor degeneration. Significant changes in response amplitude and kinetics were observed as early as post-natal day 20, and by postnatal day 45, the response amplitudes were reduced by 91%, and then remained relatively stable until six months. These functional changes correlated with the loss of rod photoreceptors and mGluR6 receptor expression. Moreover, we showed that rod bipolar cells make transient ectopic connections with cones during progression of the disease. At P45, ON-cone bipolar cells retain mGluR6 responses for longer periods than the rod bipolar cells, but by about six months, these cells also strongly down-regulate mGluR6 expression. We propose that the relative longevity of mGluR6 responses in cone bipolar cells is due to the slower loss of the cones. In contrast, ionotropic glutamate receptor expression and function in OFF-cone bipolar cells remains normal at six months despite the loss of synaptic input from cones. Thus glutamate receptor expression is differentially regulated in bipolar cells, with the metabotropic receptors being absolutely dependent on synaptic input. These findings define the temporal window over which bipolar cells may be receptive to photoreceptor repair or replacement.
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