The Microbead Occlusion Model: A Paradigm for Induced Ocular Hypertension in Rats and Mice
The Microbead Occlusion Model: A Paradigm for Induced Ocular Hypertension in Rats and Mice
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DOI：
10.1167/iovs.09-3947
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Calkins, David J.
中科院分区：
文献类型：
--
作者：
Sappington, Rebecca M.;Carlson, Brian J.;Calkins, David J.
目的。眼压升高是青光眼的重要危险因素。动物模型通常涉及手术侵入性的眼压升高技术。在这里，作者描述了一种新的相对简单的方法来诱导大鼠和小鼠高度一致、适度和可重复的眼压升高。方法：通过在大鼠(2.5-7亩L)和小鼠(1亩L)的前房内注射聚苯乙烯微球来阻断房水流出，单侧升高眼压。另一只眼接受等量的生理盐水注射作为内对照。作者使用眼压计来测量微珠引起的眼压升高。对视神经进行组织学处理以确定轴突丢失。结果：对于大鼠来说，单次注射微珠可使眼压升高21%至34%，具体取决于眼压的大小，持续约2周，尽管没有追踪到完全恢复。注射生理盐水的眼内压稳定。额外注射(5亩L)将抬高延长至8周。两次注射的累积压力暴露均呈线性增加。对于小鼠，单次注射1亩L微珠可引起高度规律性的30%的眼压升高，并持续3周以上，累积压力暴露呈线性上升。对于大鼠和小鼠来说，给定一天的动物间变异性都不大，大约是平均眼压测量的5%。延长海拔高度(4-5周)导致大鼠和小鼠大约20%的轴突丢失。结论：这些数据支持一种新的、灵活的轻度高眼压伴轴突丢失的模型。眼压升高的最大持续时间将在未来的研究中进一步确定。(投资眼科VS科学。2010年；51：207216)doi：10.1167/iovs.09-3947
PURPOSE. Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Animal models often involve techniques for IOP elevation that are surgically invasive. Here the authors describe a novel and relatively simple method for inducing a highly consistent, modest, and repeatable elevation in IOP for rats and mice.METHODS. IOP was elevated unilaterally by injection of polystyrene microbeads into the anterior chamber to occlude aqueous outflow in rats (2.5-7 mu L) and mice (1 mu L). The fellow eye received an equivalent saline injection as internal control. The authors used tonometry to measure microbead-induced IOP elevations. Optic nerves were processed histologically to determine axon loss.RESULTS. For rats, a single injection of microbeads raised IOP by 21% to 34%, depending on volume, for approximately 2 weeks, though they were not tracked to full recovery. IOP in the saline-injected eye was constant. An additional injection (5 mu L) extended the elevation to 8 weeks. Cumulative pressure exposure for both injections increased linearly. For mice, a single 1-mu L injection of microbeads elicited a highly regular 30% elevation in IOP that persisted for more than 3 weeks, with a linear rise in cumulative pressure exposure. For both rats and mice, interanimal variability on a given day was modest, approximately 5% of the mean IOP measurement. Extended elevations (4-5 weeks) induced approximately a 20% loss of axons in both rats and mice.CONCLUSIONS. These data support a novel and flexible model of modest ocular hypertension with axon loss. The maximal duration of IOP elevation will be further characterized in future studies. (Invest Ophthalmol Vis Sci. 2010;51:207-216) DOI:10.1167/iovs.09-3947