Effects of Ocular Hypotensive Agents in a Microbead-induced Mouse Model of Glaucoma

Abstract

Purpose: : Effects of Ocular Hypotensive Agents in a Microbead-induced Mouse Model of Glaucoma

Methods: : Adult C57BL/6J mice were induced to develop ocular hypertension by unilateral intracameral injection of microbeads. The effects of twice daily, topically administered Latanoprost, Pilocarpine, Timolol, Brimonidine, Brinzolamide, and vehicle control, were tested. The mice were sacrificed on day 21 post microbead injection and their whole mount retinas and optic nerves were collected. Degeneration of retinal ganglion cells (RGC) and their axons were quantitatively assessed with immunohistochemistry and electron microscopy. The retinas were imaged with spectral domain-optic coherence tomography (SD-OCT), and the thickness of ganglion cell-inner plexiform layer (GC-IPL) complex was measured.

Results: : Comparing with vehicle control group, topical application of Timolol, Brimonidine, and Brinzolamide, compounds that suppress aqueous production, showed significant reduction of IOP levels. A single dose of Timolol induced only a short term IOP-lowering effect that was statistically significant at 1 and 2 h post administration of the drug; whereas, Brimonidine and Brinzolamide induced significant IOP reduction that lasted over 24 h after drug administration. Following 2 week twice daily topical application of Timolol, Brimondine and Brinzolamide, we observed reduced loss of RGCs (28 ± 5.4%, 20 ± 3.8% and 23 ± 3.5%, respectively) and axons (21 ± 9.5%, 19 ± 8.9% and 20 ± 12%, respectively) in treated groups as compared to vehicle controls (51 ± 3.1% and 58 ± 5.4%, respectively). Accordingly, these drug-treated groups also exhibited less reduction of GC-IPL thickness comparing to the vehicle control group. In contrast, Latanoprost and Pilocarpine, the ocular hypothesive agents that act on the outflow system, failed to decrease IOP in the microbead-induced ocular hypertensive mice.

Conclusions: : The microbead-induced mouse model of ocular hypertension offers a unique model system that disrupts the outflow facility and allows selectively screening of drugs that lower IOP via reducing aqueous humor production. Measurement of GC-IPL thickness with SD-OCT can be an effective method for evaluating non-invasively RGC axon damage in the glaucoma mouse model.

Keywords: intraocular pressure • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • ganglion cells