Retinal remodeling in human retinitis pigmentosa.
Retinal remodeling in human retinitis pigmentosa.
复制标题
DOI：
10.1016/j.exer.2016.03.018
复制
发表时间：
2016-09
影响因子：
3.4
通讯作者：
Marc, R. E.
中科院分区：
文献类型：
--
作者：
Jones, B. W.;Pfeiffer, R. L.;Ferrell, W. D.;Watt, C. B.;Marmor, M.;Marc, R. E.
关键词：
视网膜色素变性（RP）是一种进行性的，目前不可逆的神经退行性疾病，通常是由基因缺陷引起的，这些基因缺陷破坏了光感受器的功能或结构。虽然RP最初可能是一种光感受器疾病，但越来越多的证据表明，随着外层视网膜退化，内层视网膜逐渐变得紊乱。这些改变在动物模型中得到了广泛的描述，但在人类中的重塑还没有得到很好的表征。这项研究，使用计算分子表型（CMP），旨在促进我们对人类视网膜重塑过程的理解。我们描述了锥介导的整体拓扑结构的保存，视网膜双极细胞中疾病的最早阶段的视网膜重编程，以及神经元和神经胶质细胞的小分子和蛋白质特征的改变。此外，虽然缪勒神经胶质细胞似乎是退化视网膜中最后留下的一些细胞，但它们也是神经视网膜中对应激做出反应的第一个细胞类别之一，这可能揭示了与其他视网膜细胞类别中的重塑和细胞死亡相关的机制。同样重要的是，视网膜网络拓扑结构发生了改变。我们的研究结果表明，假设大量保留神经视网膜的干预措施可能会在疾病的晚期失败。即使是早期干预也不能保证干预措施不会受到渐进性重塑的影响。需要在疾病进展的生物学和机制方面开展基础工作，以支持视力挽救策略。
Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.
登录
查看更多内容
影响因子：
1.8
作者：
Baehr, Wolfgang;Frederick, Jeanne M.
通讯作者：
Frederick, Jeanne M.
影响因子：
2.5
作者：
Bayley, Philippa R.;Morgans, Catherine W.
通讯作者：
Morgans, Catherine W.
影响因子：
3.4
作者：
Beltran, William A.;Wen, Rong;Aguirre, Gustavo D.
通讯作者：
Aguirre, Gustavo D.
DOI：
10.1073/pnas.0501233102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Dryja, TP;McGee, TL;Rajagopalan, AS
通讯作者：
Rajagopalan, AS
影响因子：
56.9
作者：
Allikmets, R;Shroyer, NF;Leppert, M
通讯作者：
Leppert, M