Abstract
Purpose: :
Intracameral injection of microbeads is becoming widely accepted for inducing elevation of intraocular pressure (IOP) and glaucomatous optic neuropathy in the mouse. To determine whether this method is suitable for screening ocular hypotensive agents, we evaluated the IOP-lowering effects of known ocular hypotensive agents in this model.
Methods: :
Ocular hypertension was induced unilaterally in the right eye of adult C57BL/6J mice by intracameral injection of polystyrene microbeads (5 x106/eye). IOP was monitored every other day by a TonoLab tonometer. At day 7 post-injection, one drop of vehicle, Brinzolamide (1%), Brimonidine (0.2%), Timolol (0.5%), or Latanoprost (0.005%), was topically administrated to the injected eye (n = 8 per group). IOP was monitored at 1, 2, 6 and 24 hour post-dose.
Results: :
The mean IOP of the untreated mouse eye was stable throughout the study, averaged 10.6 ± 0.6 mmHg (mean ± SD). IOP increased gradually after intracameral injection of microbeads, peaking at 20-24 mmHg on day 7 post-injection. Three of the 4 anti-glaucoma drugs evaluated, Timolol, Brimonidine, and Brinzolamide, significantly reduced mouse IOP. Timolol brought IOP to 12.2 ± 0.7 mmHg, close to a baseline level, in an hour after administration. Brimonidine reduced IOP significantly (p < 0.05) at as early as 1 hr, and the IOP reached the baseline level (11.5 ± 1.2 mmHg) at 2-6 hr. Brinzolamide induced a gradual IOP reduction, which reached 12.4 ± 1.3 mmHg at 24 hr. In contrast, Latanoprost did not affect microbead-induced IOP elevation.
Conclusions: :
These data suggest that microbead-induced ocular hypertension mouse model is useful for evaluation of pharmacological agents with certain IOP-lowering mechanisms; compounds that decrease aqueous production, but not those that affect uveoscleral outflow.
Keywords: intraocular pressure • aqueous • trabecular meshwork