The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice.

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 microL) and mice (1 microL). 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 microL) extended the elevation to 8 weeks. Cumulative pressure exposure for both injections increased linearly. For mice, a single 1-microL 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.