Establishment of an adult zebrafish model of retinal neurodegeneration induced by NMDA
Establishment of an adult zebrafish model of retinal neurodegeneration induced by NMDA
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NMDA诱导成年斑马鱼视网膜神经变性模型的建立
DOI：
10.18240/ijo.2019.08.04
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发表时间：
2019-08-18
影响因子：
1.4
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
--
作者：
Luo, Zhi-Wen;Wang, Han-Tsing;Zhang, Xu
目的：目的：建立N-甲基-D-天冬氨酸（N-Methyl-D-aspartic acid，NMDA）诱导的成年斑马鱼视网膜神经变性模型。玻璃体内注射（I. V.），和腹膜内注射（I. P.），并通过苏木精和伊红以及TUNEL染色检查经处理的斑马鱼的视网膜病理学和变性。结果：100 μ mol/L NMDA可使视网膜内层增厚，而100 μ mol/L NMDA则可使视网膜内层增厚。局腹腔注射0.5mol/L NMDA组视网膜神经节细胞层出现明显凋亡，视网膜厚度减少。16 mg/kg NMDA腹腔给药组大鼠出现癫痫样行为学改变，但未出现视网膜组织学改变。结论：3种给药方法中，静脉注射NMDA最适合建立斑马鱼视网膜急性损伤模型。I.M.与NMDA一起使用可能是用作慢性视网膜损伤模型的最佳方法。注射NMDA会导致脑损伤白藜芦醇和MK 801可能是一种有临床价值的治疗视网膜神经变性的药物。
AIM: To establish a model of retinal neurodegeneration induced by N-Methyl-D-aspartic acid (NMDA) in adult zebrafish.METHODS: We compared the effects of three different NMDA delivery methods on retinal neurodegeneration in adult zebrafish: immersion (I.M.), intravitreal injection (I.V.), and intraperitoneal injection (I.P.), and examined retinal pathology and degeneration by hematoxylin and eosin and TUNEL staining in the treated zebrafish. Effects of the NMDA receptor antagonist MK-801 and the natural product resveratrol on NMDA-induced retinal neurodegeneration were also assessed.RESULTS: The thickened inner retina was seen in histology with 100 mu mol/L NMDA by I.M. administration. Significant apoptosis in the retinal ganglion cell layer and retinal thickness reduction occurred in 0.5 mol/L NMDA I.P. administration group. Seizure-like behavioral changes, but no retinal histological alteration occurred in 16 mg/kg NMDA I.P. administration group. Resveratrol and MK-801 prevented NMDA-induced retinal neurodegeneration in the zebrafish.CONCLUSION: Among the three drug administration methods, I.V. injection of NMDA is the most suitable for establishment of an acute retinal damage model in zebrafish. I.M. with NMDA is likely the best for use as a chronic retinal damage model. I.P. treatment with NMDA causes brain damage. Resveratrol and MK801 may be a clinically valuable treatment for retinal neurodegeneration.