Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric.
Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric.
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DBA/2J小鼠的进行性神经节细胞丧失和视神经变性是可变且不对称的。
DOI：
10.1186/1471-2202-7-66
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发表时间：
2006-10-03
期刊：
影响因子：
2.4
通讯作者：
Nickells, Robert W.
中科院分区：
文献类型：
--
作者：
Schlamp, Cassandra L.;Li, Yan;Dietz, Joel A.;Janssen, Katherine T.;Nickells, Robert W.
青光眼是一种慢性视网膜神经退行性疾病，以视神经轴突变性和视网膜神经节细胞凋亡为特征。DBA/2J近交系小鼠发生慢性遗传性青光眼，是研究这种疾病的分子机制和减少视网膜神经节细胞丢失的新的治疗措施的重要模型系统。虽然这种疾病在这些小鼠身上的遗传学特征很好，但其进展的病因，特别是关于视网膜退化，还没有。我们使用了两种不同的标记技术，即轴突的死后DiI标记和βGeo报告基因的神经节细胞特异性表达，分别评估了衰老小鼠视神经变性和神经节细胞丢失的时间进程。视神经变性，以轴突丢失和胶质增生为特征，首先出现在8到9个月大的小鼠身上。退行性变似乎遵循逆行路线，轴突从其近端向球体死亡。虽然神经损伤通常是双侧的，但疾病的进展在单个小鼠的眼睛之间是不对称的。一些神经也表现出局灶性保存，一般在鼻周区域的轴突束。神经节细胞丢失，作为βGeo表达缺失的函数，在8至10个月龄的一些小鼠中明显存在，并在10.5月龄以上的大多数小鼠中普遍存在。大多数眼睛表现出整个视网膜神经节细胞的均匀丢失，但许多年轻小鼠表现出从视神经头到视网膜外围的局部细胞丢失。与我们在视神经中观察到的相似，神经节细胞的丢失通常在同一动物的眼睛之间是不对称的。对这项研究中使用的两组小鼠收集的数据进行比较后发现，这种疾病最初的损害部位是视神经的轴突，随后是神经节细胞胞体的死亡。
Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal ganglion cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the βGeo reporter gene, to evaluate the time course of optic nerve degeneration and ganglion cell loss, respectively, in aging mice. Optic nerve degeneration, characterized by axon loss and gliosis is first apparent in mice between 8 and 9 months of age. Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe. Although nerve damage is typically bilateral, the progression of disease is asymmetric between the eyes of individual mice. Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region. Ganglion cell loss, as a function of the loss of βGeo expression, is evident in some mice between 8 and 10 months of age and is prevalent in the majority of mice older than 10.5 months. Most eyes display a uniform loss of ganglion cells throughout the retina, but many younger mice exhibit focal loss of cells in sectors extending from the optic nerve head to the retinal periphery. Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal. A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma.
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影响因子：
4.5
作者：
Libby RT;Li Y;Savinova OV;Barter J;Smith RS;Nickells RW;John SW
通讯作者：
John SW
影响因子：
--
作者：
NYMAN, K;TOMITA, G;KAWAMURA, M
通讯作者：
KAWAMURA, M
视网膜神经节细胞变性是拓扑的，但在DBA/2J小鼠中不是特异性细胞类型。
影响因子：
7.8
作者：
Jakobs, Tatjana C;Libby, Richard T;Ben, Yixin;John, Simon W M;Masland, Richard H
通讯作者：
Masland, Richard H
影响因子：
--
作者：
QUIGLEY, HA;ADDICKS, EM;MAUMENEE, AE
通讯作者：
MAUMENEE, AE
影响因子：
16.2
作者：
Plump, AS;Erskine, L;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M