Monitoring Retinal Morphologic and Functional Changes in Mice Following Optic Nerve Crush
Monitoring Retinal Morphologic and Functional Changes in Mice Following Optic Nerve Crush
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DOI：
10.1167/iovs.14-13895
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发表时间：
2014-06-01
影响因子：
4.4
通讯作者：
Clark, Abbot F.
中科院分区：
文献类型：
--
作者：
Liu, Yang;McDowell, Colleen M.;Clark, Abbot F.
目的。方法采用成年BALB/CJ小鼠进行单侧视神经挤压(ONC)实验，观察视网膜电信号(ERG)对视网膜神经节细胞(RGC)功能的影响。尼氏染色检测RGC层(GCL)和上丘(SC)神经元丢失情况。用光谱域光学相干断层扫描(SD-OCT)成像评价视网膜厚度。用图形视网膜电流图和全视野闪光视网膜电流图测定视网膜功能。结果：ONC后7d和28d，GCL和对侧SC分别出现进行性神经元丢失。SD-OCT图像神经纤维层(NFL)、神经纤维层(GCL)和内丛状层(IPL)的联合厚度与GCL的细胞数呈线性相关。只有一半的正常BALB/CJ小鼠表现出典型的ERG反应，其反应比C57BL/6J小鼠小且晚。ONC减少了图形ERG和PSTR，但图形ERG的减少早于PSTR，先于GCL的解剖细胞丢失。结论ONC对PhNR和暗适应OPs无影响，SD-OCT和ERG可用于监测ONC引起的视网膜形态和功能改变。模式ERG和PSTR能够发现早期RGC功能障碍，但模式ERG表现出更高的敏感性。我们的结果支持在使用小鼠ONC模型的研究中使用这些工具。
PURPOSE. We characterized the morphologic and functional changes in optic nerve crushed mice and evaluated electroretinogram (ERG) responses as tools to monitor retinal ganglion cell (RGC) dysfunction.METHODS. We performed optic nerve crush (ONC) unilaterally in adult BALB/cJ mice. The neuronal loss in the RGC layer (GCL) and superior colliculus (SC) was determined by Nissl staining. Retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT) imaging. Retinal function was determined by pattern ERG and full-field flash ERG. Responses of pattern ERG, positive scotopic threshold response (pSTR), scotopic oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed.RESULTS. The ONC induced progressive neuronal loss in GCL and contralateral SC starting from 7 and 28 days following ONC, respectively. A linear correlation was observed between combined thickness of nerve fiber layer (NFL), GCL, and inner plexiform layer (IPL) imaged by SD-OCT and cell numbers in GCL. Only half of the normal BALB/cJ mice exhibited pattern ERG response, which was smaller and later compared to C57BL/6J mice. The ONC reduced pattern ERG and pSTR, but the reduction of pattern ERG was earlier than pSTR, preceding the anatomical cell loss in the GCL. The PhNR and scotopic OPs were not affected by ONC.CONCLUSIONS. The SD-OCT and ERG can be used to monitor noninvasively retinal morphologic and functional changes induced by ONC. Pattern ERG and pSTR are able to detect early RGC dysfunction, but pattern ERG exhibits higher sensitivity. Our results support the use of these tools in studies using the mouse ONC model.