A rat model of glaucoma induced by episcleral vein ligation
A rat model of glaucoma induced by episcleral vein ligation
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DOI：
10.1016/j.exer.2006.03.014
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发表时间：
2006-10-01
影响因子：
3.4
通讯作者：
Yoshimura, Nagahisa
中科院分区：
文献类型：
--
作者：
Yu, Saiyuu;Tanabe, Teruyo;Yoshimura, Nagahisa
为了建立一种可靠的青光眼动物模型，我们研究了在大鼠眼睛中结扎巩膜外静脉是否可以诱导眼内压（IOP）升高以及伴随的青光眼特征性形态学特征。第二天检测到IOP升高（30.1 +/-4.4 mmHg：手术眼; 21.0 +/-1.8 mmHg：对照眼），并在手术后持续至少7个月（24.5 +/-2.3 mmHg：手术眼; 19.7 +/-1.9 mmHg：对照眼）。这些结果表明，巩膜上静脉结扎可在手术后立即引起非常轻微的IOP升高，并可持续数月。此外，似乎在用巩膜外静脉结扎治疗的个体眼睛中IOP升高的模式几乎没有变化。慢性高眼压后期视网膜神经节细胞层有选择性的形态学改变，视盘凹陷明显。RGC通过凋亡性死亡而选择性丢失。RGC的数量在术后12周减少了18%，最终在术后8个月减少了35%。Muller细胞下调p27 Kip1的表达，即使在青光眼的晚期，也部分处于反应状态。碱性成纤维细胞生长因子和睫状神经营养因子的表达，这是神经营养因子参与细胞存活和神经保护的控制，在晚期显着下降。总之，这些观察结果表明，基于简单结扎程序的巩膜外静脉结扎模型可重复地提供了可靠的青光眼模型，并有助于深入了解人类青光眼的潜在分子和细胞基础，并设计针对该疾病的新药物。(c)2006爱思唯尔有限公司保留所有权利。
To establish a reliable animal model of glaucoma, we examined if episcleral vein ligation in rat eyes can induce intraocular pressure (IOP) elevation and concomitant characteristic morphological features of glaucoma. IOP elevation was detected on the next day (30.1 +/- 4.4 mmHg: operated eyes; 21.0 +/- 1.8 mmHg: control eyes) and persisted at least 7 months after the procedure (24.5 +/- 2.3 mmHg: operated eyes; 19.7 +/- 1.9 mmHg: control eyes). These results suggest that episcleral vein ligation can induce very mild IOP elevation immediately after the operation, which can last over several months. Furthermore, it appears there was little variability in the patterns of IOP elevation among the individual eyes treated with episcleral vein ligation. Morphological changes were detected selectively in the retinal ganglion cell (RGC) layer and optic disc excavation was evident in the late stage of chronic IOP elevation. RGCs were selectively lost by apoptotic death. The number of RGCs was reduced by 18% at 12 weeks and eventually by 35% at 8 months postoperatively. Muller cells downregulated the expression of p27Kip1 and appeared to be partially in a reactive state even at the advanced stages of glaucoma. The expression of basic fibroblast growth factor and ciliary neurotrophic factor, which are neurotrophic factors implicated in the control of cell survivals and neuroprotection, significantly declined at the advanced stages. Taken altogether, these observations indicate that the episcleral vein ligation model based on the simple ligation procedure reproducibly provides a reliable glaucoma model and contributes to give insights into the underlying molecular and cellular bases of human glaucoma and to devise the new medication upon the disease. (c) 2006 Elsevier Ltd. All rights reserved.