Abstract
Purpose:
We established an acute model of glaucoma in rodents using intracameral injection of microbeads to obstruct aqueous humor outflow and induce ocular hypertension (OHT). While rodent models of glaucoma have been and continue to be extremely informative, important differences in structure and function exist between rodents and primates. Inducing OHT in non-human primates (NHP) would allow us to better understand how these differences influence glaucoma pathology and progression. The purpose of this study was to establish an acute NHP model of glaucoma by injecting microbeads into the anterior chamber of squirrel monkeys.
Methods:
OHT was induced in Bolivian squirrel monkeys (SMs) via bilateral injection of 15μm or 30μm polystyrene microbeads into the anterior chamber. Intraocular pressure (IOP) was measured weekly in anesthetized SMs and 2 to 3 times weekly in awake SMs using a restraint tube system. SMs received topical Xalatan, an IOP-lowering drug, once daily two weeks post-injection.
Results:
Bilateral injection of 50μl of 15μm microbeads increased IOP in anesthetized SMs 27.8% from 16.58 ± 0.47mmHg to 21.20 ± 0.52mmHg after 6 days (p=0.002, n=3). Xalatan treatment for 2 days lowered IOP 30.6% compared to OHT (p<0.001) and 11.3% compared to baseline (p=0.181). Stopping Xalatan treatment increased IOP 32.4% compared to OHT+Xalatan and 17.5% compared to baseline (p<0.031). Weekly anesthetic events to measure IOP resulted in weight loss in most SMs. To address this we developed a physical restraint system to measure IOP in awake SMs. Using this system, injection of 40μl of 30μm microbeads elevated awake IOP 20.6% from 16.63 ± 0.22mmHg to 19.98 ± 0.28mmHg over 10 days (p<0.001, n=3). Xalatan treatment for 4 days lowered IOP 8.2% compared to OHT (p=0.010); however IOP was still elevated compared to baseline (10.4%, p=0.040). Stopping Xalatan treatment increased IOP to 9.3% compared to OHT+Xalatan and 20.6% compared to baseline (p<0.042).
Conclusions:
Microbead injection induced OHT in SMs that was alleviated with Xalatan treatment. Multiple anesthetic events produced weight loss in the majority of SMs, so a physical restraint system and training paradigm to measure IOP in awake SMs was developed. Using this model of glaucoma in SMs, we can develop a more complete view of disease progression, which in turn could provide new therapeutic targets and treatment options for patients.
Keywords: 568 intraocular pressure •
531 ganglion cells •
637 pathology: experimental