Department of Biology, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium.
Neuro-Electronics Research Flanders, 3001 Leuven, Belgium.
Int J Mol Sci. 2021 May 26;22(11):5633. doi: 10.3390/ijms22115633.
Despite being one of the most studied eye diseases, clinical translation of glaucoma research is hampered, at least in part, by the lack of validated preclinical models and readouts. The most popular experimental glaucoma model is the murine microbead occlusion model, yet the observed mild phenotype, mixed success rate, and weak reproducibility urge for an expansion of available readout tools. For this purpose, we evaluated various measures that reflect early onset glaucomatous changes in the murine microbead occlusion model. Anterior chamber depth measurements and scotopic threshold response recordings were identified as an outstanding set of tools to assess the model's success rate and to chart glaucomatous damage (or neuroprotection in future studies), respectively. Both are easy-to-measure, in vivo tools with a fast acquisition time and high translatability to the clinic and can be used, whenever judged beneficial, in combination with the more conventional measures in present-day glaucoma research (i.e., intraocular pressure measurements and post-mortem histological analyses). Furthermore, we highlighted the use of dendritic arbor analysis as an alternative histological readout for retinal ganglion cell density counts.
尽管青光眼是研究最多的眼部疾病之一,但临床转化研究至少在一定程度上受到缺乏经过验证的临床前模型和检测方法的阻碍。最受欢迎的实验性青光眼模型是小鼠微珠阻塞模型,但观察到的轻度表型、混合成功率和弱重现性促使人们需要扩展可用的检测工具。为此,我们评估了反映小鼠微珠阻塞模型中青光眼早期发病变化的各种测量方法。前房深度测量和暗适应阈值反应记录被确定为评估模型成功率和绘制青光眼损伤(或未来研究中的神经保护)的出色工具集。这两种方法都是易于测量的体内工具,具有快速采集时间和高度的临床转化性,并且可以在判断有益时与当今青光眼研究中的更传统的测量方法(即眼压测量和死后组织学分析)结合使用。此外,我们强调了树突分支分析作为视网膜神经节细胞密度计数的替代组织学检测方法的使用。