Ligation of the Pterygopalatine and External Carotid Arteries Induces Ischemic Damage in the Murine Retina
Ligation of the Pterygopalatine and External Carotid Arteries Induces Ischemic Damage in the Murine Retina
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DOI：
10.1167/iovs.11-8160
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发表时间：
2011-12-01
影响因子：
4.4
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Ogishima, Hiromi;Nakamura, Shinsuke;Hara, Hideaki
目的.本研究旨在描述由血管闭塞引起的眼部缺血性疾病的小鼠模型的功能和形态学变化。在麻醉的小鼠中，通过单侧翼腭动脉（PPA）和颈外动脉（ECA）的结扎诱导视网膜缺血。通过三种不同的方法评估眼血流和视网膜循环的变化：激光斑点血流成像、眼底成像和异硫氰酸荧光素血管造影。缺血3或5小时后再灌注5天，记录视网膜电图（ERG），并对视网膜组织学进行检查和定量。自由基清除剂依达拉奉使用该模型的效果通过ERG和组织学分析进行评价。PPA和ECA的结扎显著减少了眼血流量并使血管变窄。5小时的缺血降低了ERG的a波、b波和振荡电位振幅。缺血组神经节细胞层细胞数减少，内丛状层和内核层厚度减少。视网膜缺血引起的增加，末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）阳性细胞在内层后21小时再灌注3小时缺血和19小时再灌注5小时缺血。依达拉奉（1 mg/kg，腹腔注射）可明显减轻视网膜缺血损伤。这些发现表明，PPA和ECA都被结扎的小鼠模型可能有助于阐明视网膜缺血性疾病的病理机制，并评估靶向视网膜缺血性损伤的神经保护药物。（Invest Ophthalmol维斯科学。2011; 52：9710-9720）DOI：10.1167/iovs.11-8160
PURPOSE. This study aimed to characterize the functional and morphologic changes in a murine model of ocular ischemic disease caused by vascular occlusion.METHODS. Retinal ischemia was induced by unilateral ligation of the pterygopalatine artery (PPA) and the external carotid artery (ECA) in anesthetized mice. Changes in ocular blood flow and retinal circulation were evaluated by three different methods: laser speckle blood flow imaging, fundus imaging, and fluorescein isothiocyanate angiography. Five days after reperfusion following 3- or 5-hour ischemia, an electroretinogram (ERG) was recorded, and the retinal histology was examined and quantified. The effects of a free radical scavenger, edaravone, using the model were evaluated by ERG and histologic analysis.RESULTS. The ligation of both the PPA and the ECA significantly reduced ocular blood flow and narrowed the blood vessels. Five hours of ischemia reduced the a-wave, b-wave, and oscillatory potential amplitudes of the ERG. The number of cells in the ganglion cell layer and the thickness of both the inner plexiform layer and the inner nuclear layer were reduced in the ischemic group. Retinal ischemia caused an increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the inner layer after 21-hour reperfusion following 3-hour ischemia and 19-hour reperfusion following 5-hour ischemia. Edaravone (1 mg/kg, administered intraperitoneally) significantly reduced the retinal ischemic damage.CONCLUSIONS. These findings indicate that the murine model in which both the PPA and the ECA are ligated may be useful to clarify the pathologic mechanisms of retinal ischemic diseases and to evaluate neuroprotective drugs that target retinal ischemic injury. (Invest Ophthalmol Vis Sci. 2011; 52: 9710-9720) DOI: 10.1167/iovs.11-8160