Yu Saiyuu, Tanabe Teruyo, Yoshimura Nagahisa
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, 54 Kyoto 606-8507, Japan.
Exp Eye Res. 2006 Oct;83(4):758-70. doi: 10.1016/j.exer.2006.03.014. Epub 2006 May 16.
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. Müller 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.
为建立可靠的青光眼动物模型，我们研究了大鼠眼巩膜静脉结扎是否能诱导眼压（IOP）升高及伴随青光眼的特征性形态学改变。术后第二天检测到眼压升高（手术眼：30.1±4.4 mmHg；对照眼：21.0±1.8 mmHg），且在术后至少7个月持续存在（手术眼：24.5±2.3 mmHg；对照眼：19.7±1.9 mmHg）。这些结果表明，巩膜静脉结扎术后可立即诱导非常轻微的眼压升高，且可持续数月。此外，接受巩膜静脉结扎治疗的个体眼之间眼压升高模式的变异性似乎很小。在视网膜神经节细胞（RGC）层选择性检测到形态学改变，在慢性眼压升高后期视盘凹陷明显。RGC通过凋亡性死亡选择性丢失。术后12周RGC数量减少18%，最终在8个月时减少35%。即使在青光眼晚期，Müller细胞也下调p27Kip1的表达，且似乎部分处于反应性状态。在晚期，作为参与细胞存活控制和神经保护的神经营养因子，碱性成纤维细胞生长因子和睫状神经营养因子的表达显著下降。综上所述，这些观察结果表明，基于简单结扎程序的巩膜静脉结扎模型可重复性地提供可靠的青光眼模型，有助于深入了解人类青光眼的潜在分子和细胞基础，并为该疾病设计新的药物。
