A novel rodent model of posterior ischemic optic neuropathy.
A novel rodent model of posterior ischemic optic neuropathy.
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DOI：
10.1001/2013.jamaophthalmol.271
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发表时间：
2013-02
影响因子：
8.1
通讯作者：
Goldberg JL
中科院分区：
文献类型：
--
作者：
Wang Y;Brown DP Jr;Duan Y;Kong W;Watson BD;Goldberg JL
目的：建立可靠、可重复的大鼠后缺血性视神经病变模型，研究视神经和视网膜的细胞反应。光化学缺血诱导成年大鼠后缺血性视神经病变。用异硫氰酸-葡聚糖外渗荧光素检查视网膜和视神经血管。采用组织切片和免疫组化观察病理变化。采用氟金逆行标记法定量观察PION诱导后不同时间视网膜神经节细胞的存活情况。视神经损伤，包括局部血管渗漏、视神经水肿、海绵状变性。免疫染色数据显示小胶质细胞激活和星形胶质细胞局灶性丢失，伴有邻近的星形胶质细胞肥大。与假对照组相比，损伤后1周、2周和3周分别观察到高达23%、50%和70%的视网膜神经节细胞损失。脑源性神经营养因子和睫状体神经营养因子实验性治疗可显著预防PION大鼠视网膜神经节细胞的丢失。损伤后3周，神经营养因子的应用挽救了40%以上的视网膜神经节细胞。光化学诱导的大鼠PION是一种可复制、可靠的模拟人类PION主要特征的动物模型。该大鼠PION模型与人PION模型的特征一致，使其成为研究该病病理生理过程的理想模型，其中大部分仍有待阐明。此外，它为测试视神经病变的治疗方法提供了一个最佳模型。
To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies.