Involvement of microglia in early axoglial alterations of the optic nerve induced by experimental glaucoma
Involvement of microglia in early axoglial alterations of the optic nerve induced by experimental glaucoma
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DOI：
10.1111/jnc.14070
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发表时间：
2017-07-01
影响因子：
4.7
通讯作者：
Dorfman, Damian
中科院分区：
文献类型：
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作者：
Bordone, Melina P.;Gonzalez Fleitas, Maria F.;Dorfman, Damian
青光眼是导致失明的主要原因，其特征在于视网膜神经节细胞（RGC）损失和视神经（ON）损伤。累积的证据表明神经胶质细胞参与ON和RGC的变性。我们分析了小胶质细胞反应性的贡献，早期轴神经胶质细胞的变化，在诱导模型的高眼压。为此，每周将溶剂或硫酸软骨素（CS）注射到Wistar大鼠的眼前房中，持续不同的时间间隔。在CS注射的眼睛中，Brn3a（+）RGC的量在10周和15周（但不是6周）显著降低。6周和15周时，在CS注射眼对侧的上级丘和外侧膝状体核中观察到β亚单位霍乱毒素的顺行运输减少。在近端有髓鞘的ON观察到霍乱毒素β亚单位转运的中断。磷酸化神经丝重链免疫反应性显著降低，离子化钙结合接头分子1（+），ED 1（+）（小胶质细胞标志物）和胶质细胞酸性蛋白在高眼压6周和15周时，ON中的星形胶质细胞（+）面积和luxol坚牢蓝染色减少。通过每天用米诺环素（30 mg/kg，i.p.）持续2周，在高眼压4周后。米诺环素可防止6周高眼压诱导的钙离子结合衔接分子1（+）、艾德-1（+）和胶质细胞酸性蛋白（+）面积的增加，磷酸化神经丝重链免疫反应性和luxol固蓝染色的减少，以及顺行转运的缺陷。因此，靶向小胶质细胞的反应性可能会防止早期轴突神经胶质细胞的变化，在神经胶质瘤。
Glaucoma is a leading cause of blindness, characterized by retinal ganglion cell (RGC) loss and optic nerve (ON) damage. Cumulative evidence suggests glial cell involvement in the degeneration of the ON and RGCs. We analyzed the contribution of microglial reactivity to early axoglial alterations of the ON in an induced model of ocular hypertension. For this purpose, vehicle or chondroitin sulfate (CS) were weekly injected into the eye anterior chamber from Wistar rats for different intervals. The amount of Brn3a(+) RGC significantly decreased in CS-injected eyes for 10 and 15 (but not 6) weeks. A reduction in anterograde transport of beta-subunit cholera toxin was observed in the superior colliculus and the lateral geniculate nucleus contralateral to CS-injected eyes for 6 and 15 weeks. A disruption of cholera toxin beta-subunit transport was observed at the proximal myelinated ON. A significant decrease in phosphorylated neurofilament heavy chain immunoreactivity, an increase in ionized calcium-binding adaptor molecule 1(+), ED1(+) (microglial markers), and glial fibrillary acidic protein (astrocytes) (+) area, and decreased luxol fast blue staining were observed in the ON at 6 and 15 weeks of ocular hypertension. Microglial reactivity involvement was examined through a daily treatment with minocycline (30 mg/kg, i.p.) for 2 weeks, after 4 weeks of ocular hypertension. Minocycline prevented the increase in ionized calcium-binding adaptor molecule 1(+), ED-1(+), and glial fibrillary acidic protein(+) area, the decrease in phosphorylated neurofilament heavy-chain immunoreactivity and luxol fast blue staining, and the deficit in anterograde transport induced by 6 weeks of ocular hypertension. Thus, targeting microglial reactivity might prevent early axoglial alterations in the glaucomatous ON.