Distal axonopathy with structural persistence in glaucomatous neurodegeneration
Distal axonopathy with structural persistence in glaucomatous neurodegeneration
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DOI：
10.1073/pnas.0913141107
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发表时间：
2010-03-16
影响因子：
11.1
通讯作者：
Calkins, David J.
中科院分区：
文献类型：
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作者：
Crish, Samuel D.;Sappington, Rebecca M.;Calkins, David J.
神经元变性的早期标志是远端转运丢失和轴突病理学。青光眼涉及视神经中视网膜神经节细胞（RGC）神经元及其轴突的变性。在这里，我们表明，像其他神经变性，远端轴突损伤出现在早期小鼠青光眼。当RGC轴突终止于上级丘时，主动运输的减少遵循类似于昏迷性视力丧失的视网膜定位模式。像青光眼一样，对转运缺陷的易感性随着年龄的增长而增加，并且不一定与眼压升高相关。运输缺陷进展从远端到近端，首先出现在丘，其次是更近端的次要目标，然后是视束。运输持续通过视神经乳头，然后最终在视网膜中失败。虽然轴突变性也进展远至近端，有髓鞘的RGC轴突和它们的突触前末梢在运输失败后仍然存在于丘中。因此，远端转运丢失是退行性病变前的，可能是治疗靶点。
An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early inmouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport deficits increases with age and is not necessarily associated with elevated ocular pressure. Transport deficits progress distal-to-proximal, appearing in the colliculus first followed by more proximal secondary targets and then the optic tract. Transport persists through the optic nerve head before finally failing in the retina. Although axon degeneration also progresses distal-to-proximal, myelinated RGC axons and their presynaptic terminals persist in the colliculus well after transport fails. Thus, distal transport loss is predegenerative and may represent a therapeutic target.