Retained plsticity and substantial recovery of rod-mediated visual acuity at the visual cortex in blind adult mice with retinal dystrophy
Retained plsticity and substantial recovery of rod-mediated visual acuity at the visual cortex in blind adult mice with retinal dystrophy
复制标题
患有视网膜营养不良的成年失明小鼠视杆介导的视敏度保持可塑性并显着恢复
DOI：
10.1016/j.ymthe.2018.07.012
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发表时间：
2018
期刊：
影响因子：
12.4
通讯作者：
Nakazawa T.
中科院分区：
文献类型：
--
作者：
Nishiguchi KM;Fujita K;Tokashiki N;Komamura H;Takemoto-Kimura S;Okuno H;Bito H;Nakazawa T.
在先天性失明的视网膜营养不良患者中，了解皮质可塑性的关键时期对于成功的视觉恢复是重要的。在这项研究中，我们试图模拟儿童失明，并调查视觉通路的可塑性。为此，我们产生了双突变（Pde 6ccpfl 1/cpfl 1Gnat 1 IRD 2/IRD 2）小鼠，缺乏视杆和视锥光感受器功能，我们通过基因治疗恢复杆（GNAT 1）功能，评估他们的反应。尽管基因治疗在恢复视网膜营养不良患者的视力方面的有效性有限，但在本研究中，在小鼠的初级视皮层水平上，视力意外地成功恢复。无论治疗时年龄如何（最长16个月），视力恢复的成功（通过量化视动反应和图形视觉诱发电位的变化来定义）均已实现。在对侧视觉皮层中，带有Arc启动子驱动的报告基因dVenus的盲小鼠在治疗后也恢复了皮层可塑性，标记有Arc的光触发转录。我们的研究结果表明，由于视网膜营养不良而先天性失明的老年和年轻小鼠的两种感光机制之一的视觉回路具有显着的可塑性。
In patients born blind with retinal dystrophies, understanding the critical periods of cortical plasticity is important for successful visual restoration. In this study, we sought to model childhood blindness and investigate the plasticity of visual pathways. To this end, we generated double-mutant (Pde6ccpfl1/cpfl1Gnat1IRD2/IRD2) mice with absent rod and cone photoreceptor function, and we evaluated their response for restoring rod (GNAT1) function through gene therapy. Despite the limited effectiveness of gene therapy in restoring visual acuity in patients with retinal dystrophy, visual acuity was, unexpectedly, successfully restored in the mice at the level of the primary visual cortex in this study. This success in visual restoration, defined by changes in the quantified optokinetic response and pattern visually evoked potential, was achieved regardless of the age at treatment (up to 16 months). In the contralateral visual cortex, cortical plasticity, tagged with light-triggered transcription ofArc, was also restored after the treatment in blind mice carrying anArcpromoter-driven reporter gene,dVenus. Our results demonstrate the remarkable plasticity of visual circuits for one of the two photoreceptor mechanisms in older as well as younger mice with congenital blindness due to retinal dystrophies.