Late histological and functional changes in the P23H rat retina after photoreceptor loss

Late histological and functional changes in the P23H rat retina after photoreceptor loss
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DOI:
10.1016/j.nbd.2009.12.025
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发表时间:
2010-04-01
影响因子:
6.1
通讯作者:
Picaud, Serge
Picaud, Serge
中科院分区:
医学1区
文献类型:
--
作者:
Kolomiets, Bogdan;Dubus, Elisabeth;Picaud, Serge

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已经提出了几种策略来恢复光感受器退化后的有用视力。然而,很少有研究研究光感受器完全丧失后残留视网膜神经元的晚期解剖变化和功能状态。我们观察了P23H大鼠视网膜神经节细胞(RGCs)的进行性变性。RGC多电极阵列记录显示较低的放电率,大尺度的消失,并维持短尺度的成对关联。多达11%的视网膜节细胞表现出重复且经常相关的尖峰放电,这让人想起发育的节律活动,这种活动可以被AMPA/海人藻氨酸受体阻断而可逆地抑制。P23H大鼠的视网膜神经节细胞仍然对局部电刺激敏感,产生与正常视网膜一样的短潜伏期反应。这些结果表明,尽管存在RGC的变性,但保持活跃的RGC仍然保持其基本的生理和网络特性,并出现一些新的功能变化,如退行性疾病晚期的自发节律性活动。(C)2009 Elsevier Inc.保留所有权利。
Several strategies have been proposed to restore useful vision following photoreceptor degeneration. However, a very few studies have investigated late anatomical changes and functional state of residual retinal neurons after complete photoreceptor loss. We investigated the progressive degeneration of retinal ganglion cells (RGCs) in P23H rats. The RGC multielectrode array recordings indicated lower firing rates, disappearance of broad-scale, and maintenance of short-scale pairwise correlations. Up to 11% of RGCs displayed repetitive and often correlated spike discharges, reminiscent of developmental rhythmic activity, which could be reversibly suppressed by blockade of the AMPA/kainite glutamate receptors. RGCs in P23H rats remain sensitive to local electrical stimulation, generating short-latency responses as in the normal retina. These results provide evidence that, despite the demonstrated RGC degeneration, remaining active RGCs maintain their basic physiological and network properties with some emerging functional changes such as the spontaneous rhythmic activity in late stages of the degenerative disease. (C) 2009 Elsevier Inc. All rights reserved.