A primate model of nonarteritic anterior ischemic optic neuropathy
A primate model of nonarteritic anterior ischemic optic neuropathy
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DOI：
10.1167/iovs.07-1651
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发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
Bernstein, Steven L.
中科院分区：
文献类型：
--
作者：
Chen, Celia S.;Johnson, Mary A.;Bernstein, Steven L.
目的.非动脉炎性前部缺血性视神经病变（NAION）是一种视神经（ON）卒中，是ON相关视力突然丧失的主要原因。灵长类动物（p）NAION模型对于进一步了解临床疾病至关重要，并可提供有关其他中枢神经系统（CNS）缺血性轴突病的病理生理学信息。在目前的研究中，NAION的灵长类动物模型的开发，并对这种情况下的短期和长期的反应进行了表征。pNAION是用一种新的光栓塞机制诱导的。通过微创检测（电生理学、眼底照相、吲哚菁绿色和荧光素血管造影以及磁共振成像）评估短期和长期反应，并与组织学和免疫组化结果进行比较。诱导后1天观察到与人NAION病例中观察到的相似的视盘水肿，随后消退与视盘苍白的发展相关。诱导后3个月进行的磁共振成像（MRI）显示与ON萎缩一致的变化。电生理学研究和血管成像提示ON限制性梗死伴随后的轴突变性和选择性神经元丢失，与人类NAION相似。ON炎症在诱导后2个月在病变部位和远端部位明显，表明炎症相关的轴突重塑在ON梗死后持续较长时间。pNAION在许多方面类似于人NAION，具有视神经盘水肿，随后是视网膜神经节细胞（RGC）层中的细胞损失和ON重塑。这个模型应该是有用的评估神经保护和其他治疗策略，人类NAION以及其他缺血性过程，主要影响中枢神经系统白质束。
PURPOSE. Nonarteritic anterior ischemic optic neuropathy (NAION) is an optic nerve (ON) stroke and a leading cause of sudden ON-related vision loss. A primate (p) NAION model is crucial to further understanding of the clinical disorder and can provide information regarding the pathophysiology of other central nervous system (CNS) ischemic axonopathies. In the current study, a primate model of NAION was developed, and short-and long-term responses to this condition were characterized.METHODS. pNAION was induced with a novel photoembolic mechanism. Short-and long-term responses were evaluated by minimally invasive testing (electrophysiology, fundus photography, indocyanine green and fluorescein angiography, and magnetic resonance imaging) and compared with histologic and immunohistochemical findings.RESULTS. Optic disc edema, similar to that observed in cases of human NAION was seen 1 day after induction, with subsequent resolution associated with the development of optic disc pallor. Magnetic resonance imaging (MRI) performed 3 months after induction revealed changes consistent with ON atrophy. Electrophysiological studies and vascular imaging suggest an ON-limited infarct with subsequent axonal degeneration and selective neuronal loss similar to that seen in human NAION. ON inflammation was evident 2 months after induction at the site of the lesion and at distant sites, suggesting that inflammation-associated axonal remodeling continues for an extended period after ON infarct.CONCLUSIONS. pNAION resembles human NAION in many respects, with optic disc edema followed by loss of cells in the retinal ganglion cell (RGC) layer and ON remodeling. This model should be useful for evaluating neuroprotective and other treatment strategies for human NAION as well as for other ischemic processes that primarily affect CNS white-matter tracts.