Inflammatory demyelination induces axonal injury and retinal ganglion cell apoptosis in experimental optic neuritis
Inflammatory demyelination induces axonal injury and retinal ganglion cell apoptosis in experimental optic neuritis
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DOI：
10.1016/j.exer.2008.05.017
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发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
Rostami, Abdolmohamad
中科院分区：
文献类型：
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作者：
Shindler, Kenneth S.;Ventura, Elvira;Rostami, Abdolmohamad
视神经炎是一种视神经炎症性疾病，常发生在多发性硬化症患者中，并导致视网膜神经节细胞（RGC）损伤介导的永久性视力丧失。复发缓解型实验性自身免疫性脑脊髓炎 (EAE) 是一种多发性硬化症动物模型，视神经炎发生频率较高，且 RGC 显着损失。在当前的研究中，检查了该模型中 RGC 损失的机制，以确定炎症诱导的轴突损伤是否介导 RGC 凋亡。通过将荧光金注射到 6-7 周龄雌性 SJL/J 小鼠的上丘中来逆行标记 RGC。一周后通过蛋白脂蛋白肽免疫诱导EAE。早在免疫后9天通过组织学检查发现视神经炎，在第12天发病率达到高峰。脱髓鞘发生在炎症开始后1-2天。脱髓鞘后检测到 RGC 轴突损失，免疫后第 13 天发生显着的轴突损失。第14天，轴突损失发生在RGC体损失之前。第14天，在患有视神经炎的眼睛的神经节细胞层中也观察到凋亡细胞，但在对照眼睛中没有观察到。这些结果共同表明，在实验性视神经炎模型中，炎症细胞浸润介导脱髓鞘并导致直接轴突损伤。 RGC 因轴突损伤引发的细胞凋亡机制而死亡。可能需要在轴突损伤之前启动潜在的神经保护疗法，以防止视神经炎引起的永久性 RGC 损失，以保护神经元功能。 (C) 2008 Elsevier Ltd. 保留所有权利。
Optic neuritis is an inflammatory disease of the optic nerve that often occurs in patients with multiple sclerosis and leads to permanent visual loss mediated by retinal ganglion cell (RGC) damage. Optic neuritis occurs with high frequency in relapsing-remitting experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, with significant loss of RGCs. In the current study, mechanisms of RGC loss in this model Were examined to determine whether inflammation-induced axonal injury mediates apoptotic death of RGCs. RGCs were retrogradely labeled by injection of fluorogold into superior colliculi of 6-7 week old female SJL/J mice. EAE was induced one week later by immunization with proteolipid protein peptide. Optic neuritis was detected by inflammatory cell infiltration on histological examination as early as 9 days after immunization, with peak incidence by day 12. Demyelination Occurred 1-2 days after inflammation began. Loss of RGC axons was detected following demyelination, with significant axonal loss occurring by day 13 post-immunization. Axonal loss occurred prior to loss of RGC bodies at day 14. Apoptotic cells were also observed at day 14 in the ganglion cell layer of eyes with optic neuritis, but not in control eyes. Together these results suggest that inflammatory cell infiltration mediates demyelination and leads to direct axonal injury in this model of experimental optic neuritis. RGCs die by an apoptotic mechanism triggered by axonal injury. Potential neuroprotective therapies to prevent permanent RGC loss from optic neuritis will likely need to be initiated prior to axonal injury to preserve neuronal function. (C) 2008 Elsevier Ltd. All rights reserved.