Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury

Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury
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DOI:
10.1167/iovs.12-11522
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发表时间:
2013-05-01
影响因子:
4.4
通讯作者:
Harper, Matthew M.
Harper, Matthew M.
中科院分区:
医学2区
文献类型:
--
作者:
Mohan, Kabhilan;Kecova, Helga;Harper, Matthew M.

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目的.目的评价实验性冲击伤后视网膜和视神经的损害。健康的成年小鼠暴露于超压冲击波使用定制的爆炸室。采用图形视网膜电图(pERG)、光谱域光学相干断层扫描(OCT)和彩色瞳孔光反射技术评价冲击波暴露对视网膜和视神经功能和结构的影响。对光的瞳孔反应的评估表明,与暴露于直接冲击伤的眼睛中的基线相比,在损伤后24小时使用红光或蓝光刺激的冲击伤小鼠中最大瞳孔收缩直径减小。在冲击波暴露后,没有观察到瞳孔对光反射的长期下降。我们观察到双相pERG下降,急性损伤在冲击伤后24小时恢复,慢性损伤在冲击伤后4个月出现。此外,在损伤后3个月,与对照组相比,使用OCT观察到视网膜神经纤维层显著减少。视网膜和视神经的组织学分析显示节细胞层中细胞减少的点状区域和视神经损伤。此外,与对照组小鼠相比,急性冲击波暴露后观察到与氧化应激相关的蛋白质的显著上调。我们的研究表明,视网膜神经节细胞反应的递减可以检测到冲击伤后使用非侵入性功能和结构测试。这些客观反应可作为创伤性脑损伤后难以量化的更高CNS功能的替代试验。
PURPOSE. To evaluate retina and optic nerve damage following experimental blast injury.METHODS. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex.RESULTS. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice.CONCLUSIONS. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify.