Nuclear kinesis, neurite sprouting and abnormal axonal projections of cone photoreceptors in the aged and AMD-afflicted human retina

Nuclear kinesis, neurite sprouting and abnormal axonal projections of cone photoreceptors in the aged and AMD-afflicted human retina
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DOI:
10.1016/j.exer.2007.01.005
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发表时间:
2007-05-01
影响因子:
3.4
通讯作者:
Sullivan, Robert K. P.
Sullivan, Robert K. P.
中科院分区:
医学3区
文献类型:
--
作者:
Pow, David V.;Sullivan, Robert K. P.

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组织对损伤的反应通常是再现发育过程。我们已经研究了发育再现的解剖标志是否在老年人和amd患者视网膜的锥状光感受器中是明显的。由微管介导的细胞核径向迁移是发育中的视网膜细胞的一个特征。同样,神经突的生长是神经元发育的一个特征。我们已经检查了核运动和锥体光感受器的神经突生长是否明显。calbinin阳性的视锥光感受器核通常位于外核层的外边界,为单层体细胞。在amd视网膜中,许多细胞核移位,一些体细胞靠近外丛状层(OPL),另一些在外限制膜外,而许多细胞核存在于中间水平。许多锥体的轴突过程也是异常的,当它们投射到OPL时显示出曲折的路径,偶尔在轴突改变方向的点上出现分叉的证据。我们认为,侧突的切向延伸和原始突的快速缩回可能导致观察到的扭曲轴突投射。由于微管是神经突延伸和核运动的关键介质,我们检测了微管相关蛋白2 (MAP2)的表达,MAP2是神经突延伸的重要调节因子。在这些形态异常的细胞中观察到的MAP2的强烈表达支持了异常微管介导的重塑事件存在于AMD视网膜中,并且在较小程度上存在于正常的老年视网膜中,这使得锥状光感受器重现了发育的两个关键特征。(C) 2007 Elsevier Ltd.版权所有。
Tissues of ten respond to damage by recapitulating developmental programs. We have investigated whether anatomical signs of developmental recapitulation are evident in cone photoreceptors of the aged and AMD-afflicted human retina. Radial migration of cell nuclei mediated by microtubules is a characteristic feature of cells in the developing retina. Similarly, neurite outgrowth is a feature of developing neurons. We have examined whether nuclear kinesis and neurite outgrowth from cone photoreceptors is evident. Calbindin-positive cone photoreceptor nuclei are normally positioned as a single layer of somata at the outer border of the outer nuclear layer. In AMD-afflicted retinae, many nuclei are translocated, with some somata abutting the outer plexiform layer (OPL) and others outside the outer limiting membrane whilst many nuclei are present at intermediate levels. The axonal processes of many cones were also aberrant, displaying tortuous pathways as they projected to the OPL, with occasional evidence for bifurcation at points where the axon changed direction. We suggest that tangential extension of collateral neurites and the rapid retraction of the original process may give rise to the tortuous axonal projections observed. Since microtubules are key mediators of both neurite extension and nuclear kinesis we examined expression of microtubule associated protein 2 (MAP2) which is an important regulator of neurite extension. The strong expression of MAP2 observed in those cells with aberrant morphologies supports the notion that abnormal microtubule-mediated remodelling events are present in the AMD retina and to a lesser extent in normal aged retinas, allowing cone photoreceptors to recapitulate two key features of development. (C) 2007 Elsevier Ltd. All rights reserved.