Abstract
ObjectivesOcular hypertension is a primary risk factor for glaucoma and results in retinal ganglion cell (RGC) degeneration. Current animal models of glaucoma lack severe RGC cell death as seen in glaucoma, making assessment of physiological mediators of cell death difficult. We developed a modified mouse model of ocular hypertension whereby long-lasting elevation of intraocular pressure (IOP) is achieved, resulting in significant reproducible damage to RGCs.ResultsIn this model, microbeads are mixed with hyaluronic acid and injected into the anterior chamber of C57BL/6J mice. The hyaluronic acid allows for a gradual release of microbeads, resulting in sustained blockage of Schlemm’s canal. IOP elevation was bimodal during the course of the model’s progression. The first peak occurred 1 hours after beads injection, with an IOP value of 44.69 ± 6.00 mmHg, and the second peak occurred 6–12 days post-induction, with an IOP value of 34.91 ± 5.21 mmHg. RGC damage was most severe in the peripheral retina, with a loss of 64.1% compared to that of untreated eyes, while the midperiphery exhibited a 32.4% loss, 4 weeks following disease induction.ConclusionsThese results suggest that sustained IOP elevation causes more RGC damage in the periphery than in the midperiphery of the retina. This model yields significant and reproducible RGC degeneration.
Highlights
Glaucoma is one of the leading causes of blindness worldwide [1, 2] with an estimated 60 million people suffering from the disease [2]
intra-ocular pressure (IOP) lowering agents are the only treatment shown to have a preservative effect on the visual field in patients with glaucoma [12] [13], indicating that elevation of IOP is strongly associated with retinal ganglion cell (RGC) death in glaucoma [14]
There are a handful of established animal models of glaucoma, including genetic models as well as a few models of induced ocular hypertension, which have each significantly expanded our understanding of the molecular and cellular mechanisms involved in the disease
Summary
Glaucoma is one of the leading causes of blindness worldwide [1, 2] with an estimated 60 million people suffering from the disease [2]. The microbead methodology for this model is not complicated, the model does not induce severe inflammation, and the anterior chamber remains clear during the follow up period [21, 22] Despite these advantages, the duration of increased IOP is short and the extent of RGC and axonal damage are limited. In order to induce sustained IOP elevation with significant damage to RGCs, we modified the microbead occlusion model in C57BL/6J mice using glue. This enhanced modified model allows us to take advantage of well-established genetic manipulation platforms (e.g. knock-out strains) in mice with the added benefit of sustained IOP and a corresponding increase in RGC death. We describe the pattern of RGC damage in whole retina in detail and subsequent changes in vascular and anterior chamber system accompanied with ocular hypertension (OH)
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