Comparison of the Effects of Timolol, Brinzolamide, Brimonidine and Netarsudil in a Rabbit Model of Water Loading-Induced Ocular Hypertension.

Purpose: This study aimed to compare the intraocular pressure (IOP)-lowering effects of timolol (a β-blocker), brinzolamide (a carbonic anhydrase inhibitor), brimonidine (an α2-agonist) and netarsudil (a rho kinase inhibitor) in rabbits.

Methods: The experiments were performed on 52 female New Zealand white rabbits. The IOP was measured in normotensive rabbits and in water loading-induced ocular hypertension model rabbits. Thirty microliters of timolol, brinzolamide, brimonidine, netarsudil or saline was administered topically to the randomly chosen eye. Ocular hypertension was induced by the oral administration of 60 mL/kg of tap water.

Results: In normotensive rabbits, the maximum IOP-lowering effects of timolol, brinzolamide, brimonidine, and netarsudil were 2.9 mmHg (2 h), 5.2 mmHg (1 h), 5.7 mmHg (2 h), and 3.3 mmHg (4 h), respectively. In water loading-induced ocular hypertension model rabbits, the maximum IOP-lowering effects of timolol, brinzolamide, brimonidine, and netarsudil were 3.6, 5.0, 12.2, and 5.0 mmHg, respectively. The IOP-lowering effects of brimonidine and netarsudil were sustained until 90 min after water loading.

Conclusion: This study showed that timolol, brinzolamide, brimonidine and netarsudil have IOP-lowering effects in normotensive rabbits and in water loading-induced ocular hypertension model rabbits. In an ocular hypertension rabbit model, brimonidine and netarsudil, which promote aqueous humor outflow, exhibited stronger IOP-lowering effects than timolol and brinzolamide, which suppress aqueous humor production. These results could provide data for characterizing each medication. These data may aid in the development of new glaucoma medications through the combination of existing medications.