Vision Science Graduate Program, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama, United States.
Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States.
Invest Ophthalmol Vis Sci. 2022 Jan 3;63(1):21. doi: 10.1167/iovs.63.1.21.
Rodent and primate models are commonly used in glaucoma research; however, both have their limitations. The tree shrew (Tupaia belangeri) is an emerging animal model for glaucoma research owing in part to having a human-like optic nerve head anatomy, specifically a collagenous load-bearing lamina. However, the anterior segment anatomy and function have not been extensively studied in the tree shrew. Thus, the purpose of this study was to provide the first detailed examination of the anterior segment anatomy and aqueous outflow facility in the tree shrew.
Aqueous outflow dynamics were measured in five ostensibly normal eyes from three tree shrews using the iPerfusion system over a range of pressures. Gross histological assessment and immunohistochemistry were performed to characterize anterior segment anatomy and to localize several key molecules related to aqueous outflow.
Anterior segment anatomy in tree shrews is similar to humans, demonstrating a scleral spur, a multilayered trabecular meshwork and a circular Schlemm's canal with a single lumen. Average outflow facility was 0.193 µL/min/mm Hg (95% confidence interval, 0.153-0.244), and was stable over time. Outflow facility was more similar between contralateral eyes (approximately 5% average difference) than between eyes of different animals. No significant dependence of outflow facility on time or pressure was detected (pressure-flow nonlinearity parameter of 0.01 (95% % confidence interval, -0.29 to 0.31 CI µL/min/mm Hg).
These studies lend support to the usefulness of the tree shrew as a novel animal model in anterior segment glaucoma and pharmacology research. The tree shrew's cost, load-bearing collagenous lamina cribrosa, and lack of washout or anterior chamber deepening provides a distinct experimental and anatomic advantage over the current rodent and nonhuman primate models used for translational research.
啮齿动物和灵长类动物模型常用于青光眼研究;然而,两者都有其局限性。树鼩(Tupaia belangeri)是一种新兴的青光眼研究动物模型,部分原因是其视神经头解剖结构与人相似,特别是具有胶原承载性 lamina。然而,树鼩的眼前段解剖结构和功能尚未得到广泛研究。因此,本研究的目的是首次详细检查树鼩的眼前段解剖结构和房水流出通道。
使用 iPerfusion 系统在三只树鼩的五只看似正常的眼中测量房水流出动力学,范围为不同压力。进行大体组织学评估和免疫组织化学分析,以描述眼前段解剖结构,并定位与房水流出相关的几个关键分子。
树鼩的眼前段解剖结构与人相似,具有巩膜突、多层小梁网和具有单个腔的圆形 Schlemm 管。平均流出效率为 0.193 µL/min/mm Hg(95%置信区间,0.153-0.244),且随时间稳定。对侧眼之间的流出效率更为相似(平均差异约为 5%),而不同动物之间的眼之间则不相似。未检测到流出效率随时间或压力的显著依赖性(压力-流量非线性参数为 0.01(95%置信区间,-0.29 至 0.31 CI µL/min/mm Hg)。
这些研究支持树鼩作为新型动物模型在眼前段青光眼和药理学研究中的有用性。树鼩的成本、胶原承载性 lamina cribrosa、无冲洗或前房加深等特点,与当前用于转化研究的啮齿动物和非人类灵长类动物模型相比,具有明显的实验和解剖优势。