Molecular Changes and Vision Loss in a Mouse Model of Closed-Globe Blast Trauma
Molecular Changes and Vision Loss in a Mouse Model of Closed-Globe Blast Trauma
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DOI：
10.1167/iovs.14-14353
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发表时间：
2014-08-01
影响因子：
4.4
通讯作者：
Rex, Tonia S.
中科院分区：
文献类型：
--
作者：
Bricker-Anthony, Courtney;Hines-Beard, Jessica;Rex, Tonia S.
目的。方法：成年C57BL/6小鼠暴露于一只眼的冲击波中。进行光学相干断层扫描和组织学检查以评估视网膜和视神经的完整性。用免疫组织化学方法检测细胞死亡、氧化应激和神经胶质细胞活性。结果：在视网膜外层，眼球母细胞瘤可引起视网膜色素上皮空泡和罕见的视网膜脱离，继而导致局部细胞死亡。在BLAST后，硝基酪氨酸的标记和焦下垂(caspase-1)和坏死性下垂(受体相互作用蛋白激酶-1，-3)的标记增加，主要是在视网膜内部。Caspase-1标记主要局限于星状突起的无长突细胞。伤后28天可见少量变性轴突。尽管没有实质性的细胞死亡或ERG降低，但爆炸后视力下降。结论：随着时间的推移，氧化应激、神经炎症和细胞死亡变得越来越普遍，提示持续的神经退行性反应。视网膜外部改变已消失或仍为局灶性改变。相比之下，视网膜内部的变化更强烈，随着时间的推移，从焦点区域扩散到整个视网膜。我们的眼冲击伤模型在冲击伤后的第一个月内会导致分子变化和视力下降，尽管没有明显的眼部损伤。这种微妙的反应与一些暴露在爆炸中的退伍军人视觉缺陷的延迟表现相匹配。
PURPOSE. To characterize retinal changes and assess vision after an eye-directed air blast.METHODS. Adult C57Bl/6 mice were exposed to a blast directed at one eye. Optical coherence tomography and histology were performed to assess retina and optic nerve integrity. Cell death, oxidative stress, and glial reactivity were examined by immunohistochemistry. Visual changes were measured by ERG recordings and the optokinetic reflex.RESULTS. In the outer retina, eye blast caused retinal pigment epithelium vacuoles and rare retinal detachments followed by regional cell death. Labeling for nitrotyrosine and markers of pyroptosis (caspase-1) and necroptosis (receptor-interacting protein kinases-1, -3) increased, primarily in the inner retina, after blast. Caspase-1 labeling was restricted primarily to the starburst amacrine cells. A few degenerating axons were detected at 28 days post blast. Despite a lack of substantial cell death or decreased ERG, there was a deficit in visual acuity after blast.CONCLUSIONS. Oxidative stress, neuroinflammation, and cell death became increasingly prevalent, over time post blast suggestive of an ongoing neurodegenerative response. Outer retinal changes either resolved or remained focal. In contrast, inner retinal changes were more robust and spread from focal regions to the entire retina over time post blast. Our model of eye blast trauma causes molecular changes and a decrease in visual acuity within the first month post blast despite a lack of overt eye injury. This subtle response matches the delayed presentation of visual deficits in some blast-exposed Veterans.