Rod photoreceptors protect from cone degeneration-induced retinal remodeling and restore visual responses in zebrafish.
Rod photoreceptors protect from cone degeneration-induced retinal remodeling and restore visual responses in zebrafish.
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杆光感受器免受锥变性引起的视网膜重塑并恢复斑马鱼中的视觉反应。
DOI：
10.1523/jneurosci.2910-12.2013
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发表时间：
2013-01-30
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影响因子：
--
通讯作者：
Fadool JM
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文献类型：
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作者：
Saade CJ;Alvarez-Delfin K;Fadool JM
人类在很大程度上依赖于视锥细胞介导的视觉。然而，视杆细胞（主要的感光细胞亚型）的死亡或功能障碍导致视锥细胞的继发性丧失、视网膜回路的重塑和失明。电路的变化可能会导致视力缺陷，并破坏恢复视力的尝试。我们利用斑马鱼幼虫作为一个遗传模型，专门表征与光感受器退化在锥占主导地位的视网膜的变化。光感受器与两种类型的二级神经元形成突触，双极细胞和水平细胞。使用细胞特异性报告基因表达和突触后谷氨酸受体的免疫标记，观察到显着的重塑后，在pde 6cw 59幼虫视网膜锥变性，但不杆变性的Xops：mCFPq 13线。在成年鱼中，视杆细胞和视锥细胞的数量大致相等，而在pde 6cw 59突变体中，谷氨酸受体的表达和外丛状层的突触结构得以保留，这些曾经失明的鱼获得了视觉反应。我们建议，丰富的杆在成人保护视网膜从锥变性引起的重塑。我们测试这一假设的基因操纵的数量杆幼虫。我们发现，在lor/tbx 2bp 22 bbtl或six 7吗啉注射幼虫的杆的数量增加和均匀分布保护从pde 6cw 59诱导的继发性变化。重塑是跨物种的光感受器死亡的常见后果，并且在斑马鱼中，少数存活的光感受器提供保护以免受变性诱导的变化的观察结果提供了一种模型，用于系统分析减缓甚至防止与神经退行性疾病相关的二次恶化的因素。
Humans are largely dependent upon cone-mediated vision. However, death or dysfunction of rods, the predominant photoreceptor subtype, results in secondary loss of cones, remodeling of retinal circuitry and blindness. The changes in circuitry may contribute to the vision deficit and undermine attempts at restoring sight. We exploit zebrafish larvae as a genetic model to specifically characterize changes associated with photoreceptor degenerations in a cone-dominated retina. Photoreceptors form synapses with two types of second order neurons, bipolar cells and horizontal cells. Using cell-specific reporter gene expression and immunolabeling for postsynaptic glutamate receptors, significant remodeling is observed following cone degeneration in the pde6cw59 larval retina but not rod degeneration in the Xops:mCFPq13 line. In adults, rods and cones are present in approximately equal numbers, and in pde6cw59 mutants glutamate receptor expression and synaptic structures in the outer plexiform layer are preserved, and visual responses are gained in these once-blind fish. We propose that the abundance of rods in the adult protects the retina from cone degeneration-induced remodeling. We test this hypothesis by genetically manipulating the number of rods in larvae. We show that an increased number and uniform distribution of rods in lor/tbx2bp22bbtl or six7 morpholino-injected larvae protect from pde6cw59-induced secondary changes. The observations that remodeling is a common consequence of photoreceptor death across species, and that in zebrafish a small number of surviving photoreceptors afford protection from degeneration-induced changes provides a model for systematic analysis of factors that slow or even prevent the secondary deteriorations associated with neural degenerative disease.