Strain Specific Responses in a Microbead Rat Model of Experimental Glaucoma

A major challenge in glaucoma research is the lack of reproducible animal models of RGC and optic nerve damage, the characteristic features of this condition. We therefore examined the glaucomatous responses of two different rat strains, the Brown Norway (BN) and Lister Hooded (LH) rats, to high intraocular pressure (IOP) induced by injection of magnetic beads into the anterior chamber. Magnetic microsphere suspensions (20 µl of 5–20 mg/ml) were injected into the anterior chamber of BN (n = 9) or LH (N = 15) rats. Animals from each strain were divided into three groups, each receiving a different dose of microspheres. IOP was measured over 4 weeks using a rebound tonometer. Retinal ganglion cell (RGC) damage and function were assessed using scotopic electroretinograms (ERGs), retinal flatmounts and optic nerve histology. ANOVA and Student’s <i>t</i>-tests were used to analyse the data. A significant elevation in IOP was observed in BN rats receiving injections of 20 mg (37.18 ± 12.28 mmHg) or 10 mg microspheres/ml (36.95 ± 13.63 mmHg) when compared with controls (19.63 ± 4.29 mmHg) (<i>p</i> p p P p p Although this model was easily reproducible in BN rats, the phenotype of injury observed in LH rats was very different from that observed in BN animals. We suggest that differences in the glaucomatous response observed in these two strains may be ascribed to anatomical and physiological differences and merits further investigation.

青光眼研究的核心挑战之一，在于缺乏可重复的视网膜神经节细胞（Retinal Ganglion Cell, RGC）与视神经损伤动物模型——而这正是该疾病的典型病理特征。为此，本研究针对两种不同品系的大鼠，即布朗挪威（Brown Norway, BN）与李斯特 hooded（Lister Hooded, LH）大鼠，探究其在通过前房注射磁性微球诱导的高眼压（intraocular pressure, IOP）下的青光眼样反应。我们将20微升浓度为5–20 mg/ml的磁性微球混悬液，注射入BN组（n=9）与LH组（N=15）大鼠的前房。每个品系的受试动物均被分为3个亚组，分别接受不同剂量的微球注射。在造模后的4周内，采用回弹式眼压计监测眼压变化。通过暗适应视网膜电图（scotopic electroretinograms, ERG）、视网膜铺片与视神经组织学检查，评估视网膜神经节细胞的损伤程度与功能状态。实验数据采用方差分析（ANOVA）与Student t检验进行统计学分析。结果显示，与对照组（眼压为19.63 ± 4.29 mmHg）相比，接受20 mg/ml（37.18 ± 12.28 mmHg）或10 mg/ml（36.95 ± 13.63 mmHg）微球注射的BN大鼠眼压出现显著升高（P < 0.05）。尽管该造模方法在BN大鼠中易于重复，但LH大鼠所表现出的损伤表型与BN大鼠存在显著差异。本研究推测，两种品系大鼠的青光眼样反应差异，可能源于其解剖学与生理学特征的不同，该发现值得开展进一步的深入研究。