Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis
Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis
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DOI：
10.1016/j.neulet.2015.02.059
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发表时间：
2015-04-10
影响因子：
2.5
通讯作者：
Harada, Takayuki
中科院分区：
文献类型：
--
作者：
Guo, Xiaoli;Namekata, Kazuhiko;Harada, Takayuki
视神经炎是视神经的炎症，与多发性硬化症（MS）密切相关，多发性硬化症是一种中枢神经系统的炎症性脱髓鞘综合征。它会导致视网膜神经节细胞（RGC）死亡，并可能导致严重的视力丧失。溴莫尼定（BMD）是一种选择性α 2-肾上腺素能受体激动剂，临床上用于治疗青光眼。骨密度降低眼压，但最近的证据表明，其治疗效果也可能通过独立于眼压调节的机制介导。本研究采用MOG（35-55）诱导C57BL/6J小鼠实验性自身免疫性脑脊髓炎（EAE）视神经炎时外用BMD对视网膜变性的影响，并每日滴BMD眼液。在EAE视网膜中，RGCs的数量显著减少，BMD治疗抑制了这种作用。与组织学分析一致，BMD治疗可抑制EAE小鼠的视觉损害，提示BMD的神经保护作用具有功能意义。此外，BMD增加了EAE视网膜中碱性成纤维细胞生长因子的表达水平，特别是在Muller胶质细胞和RGCs中。我们的研究结果表明，局部给药BMD可能可用于视神经炎和青光眼期间的RGC保护。2015爱思唯尔爱尔兰有限公司版权所有。
Optic neuritis is inflammation of the optic nerve and is strongly associated with multiple sclerosis (MS), an inflammatory demyelinating syndrome of the central nervous system. It leads to retinal ganglion cell (RGC) death and can cause severe vision loss. Brimonidine (BMD) is a selective alpha 2-adrenergic receptor agonist that is used clinically for the treatment of glaucoma. BMD lowers intraocular pressure, but recent evidence suggests that its therapeutic efficacy may also mediate through mechanisms independent of modulation of intraocular pressure. In this study, we examined the effects of topical administration of BMD on retinal degeneration during optic neuritis in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE was induced with MOG(35-55) in C57BL/6J mice and BMD eyedrops were applied daily. In the EAE retina, the number of RGCs was significantly decreased and this effect was suppressed with BMD treatment. Consistent with histological analyses, the visual impairment observed in EAE mice was inhibited with BMD treatment, indicating the functional significance of the neuroprotective effect of BMD. Furthermore, BMD increased the expression level of basic fibroblast growth factor in the EAE retina, particularly in Muller glial cells and RGCs. Our findings suggest that topical administration of BMD may be available for RGC protection during optic neuritis, as well as for glaucoma. (C) 2015 Elsevier Ireland Ltd. All rights reserved.