Enhancement of ON-bipolar cell responses of cone electroretinograms in rabbits with the Pro347Leu rhodopsin mutation.
Enhancement of ON-bipolar cell responses of cone electroretinograms in rabbits with the Pro347Leu rhodopsin mutation.
复制标题
Pro347Leu 视紫红质突变兔锥体视网膜电图 ON-双极细胞反应的增强。
DOI：
10.1167/iovs.11-7611
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Kurosaka D.
中科院分区：
文献类型：
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作者：
Nishimura T;Machida S;Kondo M;Terasaki H;Yokoyama D;Kurosaka D.
目的：为了确定在携带Pro347 Leu视紫红质突变的兔（Tg兔）中感光细胞变性后视网膜加工的不同阶段如何改变。锥视网膜电图（ERG）引起的150 ms的持续时间刺激13 Tg兔在12和24周龄。玻璃体内注射柠檬酸河豚毒素（TTX）+N-甲基-dl-天冬氨酸（NMDA），加入2-氨基-4-磷酸丁酸（APB），然后加入顺式-2，3-哌啶二羧酸（PDA）或6-氰基-7-硝基喹喔啉-2，3-二酮（CNQX），前后进行ERG记录。从注射前的ERG数字减去注射后的ERG，用于提取被这些药物阻断的成分。13只年龄匹配的野生型（WT）家兔采用相同的方案进行研究。在转基因兔中，由中等强度诱发的视锥ERG具有去极化模式。在12周龄时，Tg兔的ERG中反映的光感受器和关闭双极/水平细胞反应与WT兔的无显著差异。与WT兔相比，药物阻断后记录的ON双极细胞和三级神经元反应在Tg兔中显著增强。在24周龄时，Tg兔的ERG波形代表光感受器和OFF双极/水平细胞反应显著降低，但那些代表ON双极细胞和三级神经元反应的波形仍然保留。结论：在Pro347 Leu Tg兔中观察到去极化的锥状ERG反应模式。ERG中ON双极细胞反应的增强或保留有助于Tg兔波形的形成。在该模型中，ON通路的功能改变发生在视锥光感受器功能恶化之前。
Purpose.: To determine how the different stages of retinal processing change after photoreceptor degeneration in rabbits carrying the Pro347Leu rhodopsin mutation (Tg rabbits).Methods.: Cone electroretinograms (ERGs) were elicited by 150-ms duration stimuli from 13 Tg rabbits at 12 and 24 weeks of age. The ERG recordings were made before and after an intravitreal injection of tetrodotoxin citrate (TTX) plus N-methyl-dl-aspartic acid (NMDA), with the addition of 2-amino-4-phosphonobutyric acid (APB) and then cis-2, 3-piperidine-dicarboxylic acid (PDA) or 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX). Digital subtraction of the ERG after the injection from the ERG before the injection was used to extract the components that were blocked by these drugs. Thirteen age-matched, wild-type (WT) rabbits were studied with the same protocol.Results.: In Tg rabbits, the cone ERGs elicited by intermediate intensities had a depolarizing pattern. At 12 weeks of age, the photoreceptor and OFF-bipolar/horizontal cell responses reflected in the ERG in the Tg rabbits did not differ significantly from those in the WT rabbits. The ON-bipolar cells and the third-order neuronal responses recorded after pharmacologic blockade were significantly enhanced in the Tg rabbits compared with those recorded in the WT rabbits. At 24 weeks of age, the ERG waveforms representing the photoreceptors and OFF-bipolar/horizontal cell responses were significantly decreased, but those representing the ON-bipolar cell and third-order neuronal responses were still preserved in the Tg rabbits.Conclusions.: A depolarizing pattern of the cone ERG responses was seen in Pro347Leu Tg rabbits. The enhancement or preservation of the ON-bipolar cell response in the ERGs contributed to shaping the waveform in the Tg rabbits. In this model, the functional alterations in the ON-pathway took place before the deterioration of cone photoreceptor function.