Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China
JAMA Ophthalmol. 2013 Feb;131(2):194-204. doi: 10.1001/2013.jamaophthalmol.271.
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.
建立一种可靠、可重现的大鼠后部缺血性视神经病变（PION）模型，并研究视神经和视网膜的细胞反应。
通过光化学诱导缺血诱导成年大鼠发生后部缺血性视神经病变。通过荧光素异硫氰酸酯-葡聚糖外渗来检查视网膜和视神经血管。组织切片和免疫组织化学用于研究病理变化。通过荧光金逆行标记来定量研究 PION 诱导后不同时间（有无神经营养应用）的视网膜神经节细胞存活情况。
PION 诱导后证实了视神经损伤，包括局部血管渗漏、视神经水肿和海绵状变性。免疫染色数据显示小胶质细胞活化和局灶性星形胶质细胞丢失，伴有相邻星形胶质细胞肥大。与假手术对照组相比，损伤后 1 周、2 周和 3 周分别观察到 23%、50%和 70%的视网膜神经节细胞丢失。实验性脑源性神经营养因子和睫状神经营养因子治疗显著预防了 PION 大鼠的视网膜神经节细胞丢失。损伤后 3 周，神经营养因子的应用可使超过 40%的视网膜神经节细胞存活。
通过光化学诱导缺血建立的大鼠 PION 是一种可重现的可靠动物模型，可模拟人类 PION 的关键特征。
该大鼠 PION 模型的特征与人类 PION 的特征非常吻合，使其成为研究疾病病理生理过程的理想模型，其中大部分仍有待阐明。此外，它为测试治疗视神经病变的方法提供了最佳模型。
