A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture
A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture
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DOI：
10.1167/iovs.16-20576
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Flanagan, John G.
中科院分区：
文献类型：
--
作者：
Liu, Hsin-Hua;Flanagan, John G.
目的。利用先前为大鼠开发的缝合技术，通过诱导眼内压（IOP）升高，建立小鼠慢性高眼压模型。C57BL/6小鼠在麻醉（氯胺酮/噻嗪）下单眼缘缘缝合（10/0）放置。缝线放置12周（n = 10）。对照组给予相同治疗，第1天取下（n = 10）。测量两组患者眼压、视网膜电图（ERG）、光学相干断层扫描（OCT），随访12周。在第12周，对动物实施安乐死，取视网膜进行组织学评估。在延长缝线放置组，IOP在缝线植入后立即从14.3 +/- 0.9上升到48.4 +/- 4.8 mm Hg。第1天降至33.2 +/- 3.7 mm Hg，并持续升高12周。在拆线组，IOP在拆线后一天内恢复到基线水平。在IOP升高时间延长的组中，视网膜神经节细胞（RGC）介导的ERG反应继续加剧，并在第12周显著降低（P < 0.001）。视网膜神经纤维层逐渐丧失，并在第4周出现显著性变化（P < 0.001）。在第12周，RGCs显著减少（P < 0.001）。IOP正常化组ERG、OCT、RGC计数未见明显变化。环缘缝合入路在小鼠中产生轻度慢性IOP升高。模型诱导下的功能和结构变化在很大程度上与初始眼压峰值无关。
PURPOSE. To develop a chronic ocular hypertension mouse model by inducing intraocular pressure (IOP) elevation using a suture technique previously developed for rats.METHODS. C57BL/6 mice were given monocular circumlimbal suture (10/0) placement under anesthesia (ketamine/xylazine). The suture was left in place for 12 weeks (n = 10). A control group had the same treatment while it was removed after day 1 (n = 10). Intraocular pressure, electroretinogram (ERG), and optical coherence tomography (OCT) were measured in both groups for 12 weeks. At week 12, animals were euthanized and retina was harvested for histologic assessment.RESULTS. In the group with extended suture placement, IOP spiked from 14.3 +/- 0.9 to 48.4 +/- 4.8 mm Hg immediately after suture implantation. At day 1, it declined to 33.2 +/- 3.7 mm Hg and remained elevated for 12 weeks. In the suture removal group, IOP normalized to baseline within a day following suture removal. In the group with prolonged IOP elevation, the retinal ganglion cell (RGC) mediated ERG responses continued to exacerbate and were significantly reduced by week 12 (P < 0.001). Progressive loss of retinal nerve fiber layer was found and it became significant from week 4 (P < 0.001). At week 12, significant loss of RGCs (P < 0.001) was noted. In the IOP normalization group, no alteration in ERG, OCT, and RGC counting was observed.CONCLUSIONS. The circumlimbal suture approach produces a mild chronic IOP elevation in mice. Functional and structural changes under model induction are largely independent of the initial IOP spike.