Glial coverage in the optic nerve expands in proportion to optic axon loss in chronic mouse glaucoma.
Glial coverage in the optic nerve expands in proportion to optic axon loss in chronic mouse glaucoma.
复制标题
DOI：
10.1016/j.exer.2016.01.014
复制
发表时间：
2016-09
影响因子：
3.4
通讯作者：
Vetter ML
中科院分区：
文献类型：
--
作者：
Bosco A;Breen KT;Anderson SR;Steele MR;Calkins DJ;Vetter ML
在白色物质内，神经变性引起的轴突损失与神经胶质细胞基因表达、结构和功能的变化相关联，通常称为神经胶质增生。最近，我们描述了高度可变的扩大神经胶质增生的退行性视神经从DBA/2 J小鼠模型的慢性，年龄相关性青光眼。在这里，估计和比较的水平轴突损失与扩大的神经胶质覆盖和轴突变性的DBA/2 J神经，我们结合半自动轴突计数与基于阈值的分割的总胶质/瘢痕面积和变性轴突轮廓塑料横截面。在从轻度到严重变性的神经中，我们发现轴突脱落的进展与胶质细胞面积的增加相关联。我们检测到轴突损失和胶质细胞和瘢痕的聚集体覆盖之间的强相关性，而轴突损失与小部分退化的配置文件没有相关性。低至中等水平的轴突损失的神经表现出中度胶质反应，包括肥大的星形胶质细胞，激活的小胶质细胞和正常分布的少突胶质细胞，组织结构的重组最小。与此相反，广泛的轴突损失的神经表现出普遍的神经重排，轴突束领土和扩大或几乎连续的胶质和疤痕域，含有反应性星形胶质细胞，少突胶质细胞和活化的小胶质细胞的损失。这些研究结果支持视神经胶质扩张作为与轴突损失相关的视神经病变的定量估计的价值，适用于对小鼠慢性青光眼中视神经损伤的严重程度进行分级。
Within the white matter, axonal loss by neurodegeneration is coupled to glial cell changes in gene expression, structure and function commonly termed gliosis. Recently, we described the highly variable expansion of gliosis in degenerative optic nerves from the DBA/2J mouse model of chronic, age-related glaucoma. Here, to estimate and compare the levels of axonal loss with the expansion of glial coverage and axonal degeneration in DBA/2J nerves, we combined semiautomatic axon counts with threshold-based segmentation of total glial/scar areas and degenerative axonal profiles in plastic cross-sections. In nerves ranging from mild to severe degeneration, we found that the progression of axonal dropout is coupled to an increase of gliotic area. We detected a strong correlation between axon loss and the aggregate coverage by glial cells and scar, whereas axon loss did not correlate with the small fraction of degenerating profiles. Nerves with low to medium levels of axon loss displayed moderate glial reactivity, consisting of hypertrophic astrocytes, activated microglia and normal distribution of oligodendrocytes, with minimal reorganization of the tissue architecture. In contrast, nerves with extensive axonal loss showed prevalent rearrangement of the nerve, with loss of axon fascicle territories and enlarged or almost continuous gliotic and scar domains, containing reactive astrocytes, oligodendrocytes and activated microglia. These findings support the value of optic nerve gliotic expansion as a quantitative estimate of optic neuropathy that correlates with axon loss, applicable to grade the severity of optic nerve damage in mouse chronic glaucoma.