Luo Zhi-Wen, Wang Han-Tsing, Wang Ning, Sheng Wei-Wei, Jin Ming, Lu Ye, Bai Yi-Jiang, Zou Su-Qi, Pang Yu-Lian, Xu Hong, Zhang Xu
Affiliated Eye Hospital of Nanchang University; Jiangxi Research Institute of Ophthalmology & Visual Science, Nanchang 330006, Jiangxi Province, China.
Queen Mary School of Nanchang University, Nanchang 330031, Jiangxi Province, China.
Int J Ophthalmol. 2019 Aug 18;12(8):1250-1261. doi: 10.18240/ijo.2019.08.04. eCollection 2019.
To establish a model of retinal neurodegeneration induced by N-Methyl-D-aspartic acid (NMDA) in adult zebrafish.
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.
The thickened inner retina was seen in histology with 100 µmol/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.
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.
建立成年斑马鱼中由N-甲基-D-天冬氨酸（NMDA）诱导的视网膜神经变性模型。
我们比较了三种不同的NMDA给药方法对成年斑马鱼视网膜神经变性的影响：浸泡（I.M.）、玻璃体内注射（I.V.）和腹腔注射（I.P.），并通过苏木精-伊红染色和TUNEL染色检查处理后斑马鱼的视网膜病理和变性情况。还评估了NMDA受体拮抗剂MK-801和天然产物白藜芦醇对NMDA诱导的视网膜神经变性的影响。
通过I.M.给予100 μmol/L NMDA时，组织学检查可见内层视网膜增厚。腹腔注射0.5 mol/L NMDA组视网膜神经节细胞层出现明显凋亡且视网膜厚度减小。腹腔注射16 mg/kg NMDA组出现类似癫痫的行为变化，但视网膜组织学无改变。白藜芦醇和MK-801可预防斑马鱼中NMDA诱导的视网膜神经变性。
在这三种给药方法中，I.V.注射NMDA最适合在斑马鱼中建立急性视网膜损伤模型。I.M.给予NMDA可能最适合用作慢性视网膜损伤模型。腹腔注射NMDA会导致脑损伤。白藜芦醇和MK801可能是临床上治疗视网膜神经变性的有价值的药物。
