Purpose: To further characterize the microbead-induced ocular hypertensive (OHT) mouse model and investigate its potential use for preclinical screening and evaluation of ocular hypotensive agents, we tested the effects of several major anti-glaucoma drugs.
Methods: Adult C57BL/6J mice were induced to develop OHT unilaterally by intracameral injection of microbeads. The effects of the most commonly used ocular hypotensive drugs including timolol, brimonidine, brinzolamide, pilocarpine, and latanoprost on intraocular (IOP) and glaucomatous neural damage were evaluated. Degeneration of retinal ganglion cells (RGCs) and optic nerve axons were quantitatively assessed using immunofluorescence labeling and histochemistry. Thickness of ganglion cell complex (GCC: combined thickness of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer) was also assessed with spectral domain-optic coherence tomography (SD-OCT).
Results: Microbead-induced OHT model promptly responded to drugs such as timolol, brimonidine, and brinzolamide that lower IOP through suppressing aqueous humor production and showed improved RGC and axon survival as compared to vehicle controls. Accordingly, SD-OCT detected significantly less reduction of GCC thickness in mice treated with all three aqueous production suppressants as compared to vehicle-treated group. In contrast, drugs that increase aqueous outflow, such as pilocarpine and latanoprost, failed to decrease IOP in the microbead-induced OHT mice.
Conclusions: Microbead-induced OHT mice carry dysfunctional aqueous outflow facility and therefore offer a unique model that allows selective screening of aqueous production suppressant anti-glaucoma drugs or for studying the mechanisms regulating aqueous humor production. Our data set the stage for using GCC thickness assessed by SD-OCT as an imaging biomarker for non-invasive tracking of neuronal benefits of glaucoma therapy in this model. |
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