Developmental abnormalities in the Nuc1 rat retina: A spontaneous mutation that affects neuronal and vscular remodeling and retinal function
Developmental abnormalities in the Nuc1 rat retina: A spontaneous mutation that affects neuronal and vscular remodeling and retinal function
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DOI：
10.1016/j.neuroscience.2005.08.084
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Sinha, D
中科院分区：
文献类型：
--
作者：
Gehlbach, P;Hose, S;Sinha, D
视网膜是研究脊椎动物中枢神经系统发育的极佳模型。我们在Spraogue-Dawley大鼠身上发现了一种自发突变，导致了一种新颖而不寻常的眼部表型，包括视网膜异常，我们将其命名为Nucl。我们之前已经证明，Nucl突变似乎抑制了发育中的视网膜中的程序性细胞死亡。在这里，我们报告了核纯合子大鼠视网膜神经元和视网膜血管的成熟都是异常的。视网膜神经元和血管系统的发育变化与异常程度有关。随着核纯合子的成熟，局灶性视网膜脱离在出生后大约3个月就开始了，而与视网膜前纤维化和新生血管相关的近全牵引性视网膜脱离在18个月时就很明显了。2.5月龄时的视网膜电图研究表明，功能性视网膜变性先于视网膜脱离。这种功能异常在视杆和视网膜内最为明显，并存在于纯合子突变体中，但不存在杂合子突变体中。视杆和视锥感光细胞的免疫细胞化学研究表明，在核纯合子中，视杆感光细胞异常，而不是视锥感光细胞，这与视网膜电图仪的发现一致。在核动物中，穆勒细胞被激活。虽然这种激活可能是由炎症引起的，但Nucl中的Muller细胞可能是对神经元的影响做出反应。看起来，核突变起到了一个调节作用--
The retina serves as an excellent model in which to study vertebrate CNS development. We have discovered a spontaneous mutation in the Sprague-Dawley rat that results in a novel and unusual ocular phenotype, including retinal abnormalities, that we have named Nucl. We have previously shown that the Nucl mutation appears to suppress programmed cell death in the developing retina. Here we report that maturation of both the retinal neurons and the retinal vessels is abnormal in Nucl homozygous rats. The developmental changes in the retinal neurons and vasculature are correlated with regard to degree of abnormality. As Nucl homozygotes mature, focal retinal detachment begins at approximately 3 months after birth, and near total traction retinal detachment, associated with pre-retinal fibrosis and neovascularization, is evident by 18 months. Electroretinographic studies at 2.5 months of age indicate that functional retinal degeneration precedes retinal detachment. The functional abnormality is most evident in rods and the inner retina, and is present in homozygous but not heterozygous mutants. Immunocytochemical studies of rod and cone photoreceptors indicate abnormalities in rod, but not cone, photoreceptors in Nucl homozygotes, consistent with the electroretinographic findings. In Nucl animals, the Muller cells are activated. Although such activation may result from inflammation, Muller cells in Nucl may be reacting to a neuronal influence. It appears that the Nucl mutation plays a reg-