Comparative analysis of retinal ganglion cell damage in three glaucomatous rat models
Comparative analysis of retinal ganglion cell damage in three glaucomatous rat models
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三种青光眼大鼠模型视网膜神经节细胞损伤的比较分析
DOI：
10.1016/j.exer.2018.03.019
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发表时间：
2018-07-01
影响因子：
3.4
通讯作者：
Wu, Jihong
中科院分区：
文献类型：
--
作者：
Huang, Wanjing;Hu, Fangyuan;Wu, Jihong
进行性视网膜神经节细胞（RGC）死亡是青光眼视网膜神经纤维层变薄和视野缺损的主要原因。本研究的目的是比较三种常用青光眼大鼠模型的 RGC 损伤。这些模型是通过以下方式生成的：（i）将顺磁微珠注入前房； (ii) 烧灼眼睛的三个巩膜外静脉 (EVC)； (iii) 玻璃体内注射 N-甲基-D-天冬氨酸 (NMDA)。在第6、12和18小时用回弹眼压计测量眼压（IOP）； 1、3、5 天；以及 1、2、3、4、6 和 8 周。我们通过免疫荧光测量了三种青光眼模型平装视网膜中的 RGC 密度。随后，通过视网膜切片的苏木精和伊红染色来分析视网膜神经节细胞层（GCL）和视网膜内层（IRL）的厚度。通过测量不同模型的明视阴性反应（PhNR）来评估视功能恶化情况。三周的平均眼压分别为22.35 +/- 1.23 mmHg（平均值+/- SD）、20.91 +/- 1.97 mmHg和9.67 +/- 0.42 mmHg，其中RGC损失50.2%、44.00%和66.76% 8微珠组、EVC组和NMDA组分别为周。所有三组中均观察到 GCL 厚度减少，而 EVC 和 NMDA 组中 IRL 和 ONL 厚度减少。微珠和 EVC 模型均证明 RGC 损失率与 Delta IOP 积分呈显着正相关。此外，我们发现 NMDA 组的 PhNR 振幅在第一天就下降了，EVC 组在 5 天后，微珠组在 7 天后就下降了。每种青光眼大鼠模型都有其优点和缺点。我们的研究为选择合适的动物模型来推进青光眼研究提供了详细的数据。
Progressive retinal ganglion cell (RGC) death is the major cause of retinal nerve fiber layer thinning and visual field defects in glaucoma. The purpose of this study was to compare RGC damage in three commonly used glaucomatous rat models. These models were generated by (i) injection of paramagnetic microbeads into the anterior chamber; (ii) cauterization of three episcleral veins of the eye (EVC); and (iii) intravitreal injection of N-Methyl-D-Aspartate (NMDA). Intraocular pressure (IOP) was measured with a rebound tonometer at 6, 12, and 18h; 1, 3, and 5 days; and 1, 2, 3, 4, 6, and 8 weeks. We measured the RGC density of the three glaucomatous models in the flat-mounted retina by immunofluorescence. Subsequently, the thicknesses of both retinal ganglion cell layer (GCL) and inner retinal layer (IRL) were analyzed by hematoxylin and eosin staining of retinal sections. The visual functional deterioration was evaluated by measurement of the photopic negative response (PhNR) of different models.The IOP averages during three weeks were 22.35 +/- 1.23 mmHg (mean +/- SD), 20.91 +/- 1.97 mmHg, and 9.67 +/- 0.42 mmHg, with 50.2%, 44.00% and 66.76% RGC loss by 8 weeks, respectively, in the microbead group, EVC group and NMDA group. Decreased thickness in the GCL was observed in all three groups, while the thickness of IRL and ONL was decreased in the EVC and NMDA groups. Significant positive correlation of RGC loss rate with Delta IOP integral were demonstrated in both microbead and EVC models. Moreover, we found that the PhNR amplitudes declined early by the first day in the NMDA group, 5 days later in the EVC group and by 7 days in the microbead group. Each glaucomatous rat model has its strength and weakness. Our study provides detailed data for choosing suitable animal models to advance glaucoma research.