Laser-Induced Ocular Hypertension in Albino CD-1 Mice

Laser-Induced Ocular Hypertension in Albino CD-1 Mice
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DOI:
10.1167/iovs.09-4324
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发表时间:
2010-02-01
影响因子:
4.4
通讯作者:
Sretavan, David
Sretavan, David
中科院分区:
医学2区
文献类型:
--
作者:
Fu, Christine T.;Sretavan, David

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目的.目的建立白化病CD-1小鼠激光诱导高眼压(LIOH)模型,并探讨其病理过程。在CD-1小鼠中,通过激光光凝角膜缘和巩膜外静脉270至300周向诱导LIOH,保留鼻侧和睫状长动脉。用回弹眼压计测量IOP。苏木精和伊红染色的塑料切片用于视网膜层的形态计量分析,并且视网膜整体包封用抗Brn-3b免疫染色以定量视网膜神经节细胞(RGC)基因表达离子和密度。使用适当的抗体表征轴突和髓鞘形态,并从对苯二胺染色的视神经切片获得轴突计数。LIOH导致IOP在激光治疗后4小时内加倍,7天后恢复正常。早在治疗后4天,在视神经乳头(ONH)检测到轴突退行性变化、反应性可塑性和异常再生。到第7天,有髓鞘视神经的轴突数量显著减少,同时出现髓鞘降解的迹象。第14天,Brn-3b(+)RGC密度降低,神经元损失仅限于RGC层,对其他视网膜层没有明显影响。结论。激光光凝角膜缘和巩膜外静脉诱导白化病CD-1小鼠一过性高眼压。随后发生的视网膜和视神经病理事件概括了青光眼的关键特征,并将ONH RGC轴突反应作为损伤的早期表现。白化病小鼠的LIOH可作为研究RGC和轴突损伤机制的小鼠模型。(Invest Ophthalmol维斯科学。2010; 51:980-990)DOI:10.1167/iovs.09-4324
PURPOSE. To establish a laser-induced model of ocular hypertension (LIOH) in albino CD-1 mice and to characterize the sequence of pathologic events triggered by intraocular pressure (IOP) elevation.METHODS. LIOH was induced unilaterally in CD-1 mice by laser photocoagulation of limbal and episcleral veins 270 to 300 circumferentially, sparing the nasal aspect and the long ciliary arteries. IOP was measured with a rebound tonometer. Hematoxylin and eosin-stained plastic sections were used for morphometric analysis of retinal layers, and retinal whole-mounts were immunostained with anti-Brn-3b to quantify retinal ganglion cell (RGC) gene expression ion and density. Axonal and myelin morphologies were characterized using appropriate antibodies, and axon counts were obtained from paraphenylenediamine-stained optic nerve sections.RESULTS. LIOH resulted in IOP doubling within 4 hours after laser treatment, which returned to normal by 7 days. Axon degenerative changes, reactive plasticity, and aberrant regrowth were detected at the optic nerve head (ONH) as early as 4 days after treatment. By 7 days, axon number was significantly reduced in the myelinated optic nerve, with concurrent signs of myelin degradation. At 14 days, Brn-3b(+) RGC density was reduced, with neuronal loss confined to the RGC layer and no apparent effects on other retinal layers.CONCLUSIONS. Laser photocoagulation of limbal and episcleral veins induces transient ocular hypertension in albino CD-1 mice. The ensuing retinal and optic nerve pathologic events recapitulated key features of glaucoma and placed ONH RGC axon responses as an early manifestation of damage. LIOH in albino mice may be useful as a mouse model to examine mechanisms of RGC and axon glaucomatous injury. (Invest Ophthalmol Vis Sci. 2010; 51: 980-990) DOI:10.1167/iovs.09-4324