Development of Primary Open Angle Glaucoma-Like Features in a Rhesus Macaque Colony From Southern China

Abstract

Purpose To describe the ocular phenotype of spontaneous glaucoma in a non-human primate colony. Methods In total, 722 Rhesus macaque monkeys aged 10 to 25 years underwent optical coherence tomography (OCT), fundus photography (FP), and intraocular pressure (IOP) measurements. Monkeys with baseline cup-to-disc ratio (CDR) <0.5 were used to establish baseline ocular features. A subset was followed longitudinally for three years and compared to glaucoma suspects on the basis of OCT/FP criteria. Results The average IOP under ketamine sedation and average CDR for the entire colony was 13.0 ± 4.3 mm Hg and 0.38 ± 0.07, respectively. The mean baseline conscious IOP of glaucoma suspects (N = 18) versus controls (N = 108) was 16.2 ± 3.5 mm Hg and 13.9 ± 2.3 mm Hg, respectively ( P = 0.001). All glaucoma suspects had unremarkable slit lamp examinations and open angles based on anterior segment OCT. Baseline global circumpapillary retinal nerve fiber layer (RNFL) thickness was 91.5 ± 11.0 µM versus 102.7 ± 8.5 µM in suspects and controls, respectively ( P < 0.0001). All sectors on the baseline circumpapillary OCT showed a significant reduction in RNFL thickness versus controls ( P ≤ 0.0022) except for the temporal sector ( P ≥ 0.07). In three-year longitudinal analysis, neither CDR nor OCT parameters changed in controls (N = 40; P ≥ 0.16), whereas significant increase in CDR ( P = 0.018) and nominally significant decreases in two OCT sectors (nasal, P = 0.023 and nasal inferior, P = 0.046) were noted in suspects. Conclusions Members of a nonhuman primate colony exhibit important ophthalmic features of human primary open-angle glaucoma. Translational Relevance Identification of a spontaneous model of glaucoma in nonhuman primates represents an unprecedented opportunity to elucidate the natural history, pathogenesis and effective therapeutic strategies for the disease.

Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension

“…Six eyes from three monkey models successfully established COHT ( Figure 3 A), and two eyes from one monkey were set as blank controls. The baseline IOP was 13.50 ± 2.51 mmHg, which was similar to those of previous studies ( Lin et al., 2021 ; Pasquale et al., 2021 ; Quigley and Hohman, 1983 ; Tu et al., 2019 ). There was no elevated IOP in any eye after the first LP, and fluctuating IOP appeared after the second LP.…”

“…The baseline mean IOP of the rhesus monkeys was similar to that of humans ( Lin et al., 2021 ; Pasquale et al., 2021 ). If the IOP was not consistently higher than 21 mmHg, additional LP was performed again at intervals of three weeks until stable IOP was obtained.…”

“…Nonhuman primates, which are homologous with humans, constitute an indispensable laboratory model for various fields of biomedical research ( Evans and Silvestri, 2013 ; Roelfsema and Treue, 2014 ; Tomalka et al., 2021 ; Wegener et al., 2021 ), and have become ideal glaucoma experimental animals because of their highly consistent anatomical structure and physiological characteristics with humans eyeballs ( Pasquale et al., 2021 ; Rasmussen and Kaufman, 2005 ; Stewart et al., 2011 ). There are several kinds of chronic ocular hypertension (COHT) model in nonhuman primates, including topical dexamethasone treatment (steroid-induced glaucoma), intracameral injection of microbeads made of different materials, and laser photocoagulation (LP) of the trabecular meshwork (TM) ( Fingert et al., 2001 ; Pelzel et al., 2006 ; Quigley and Hohman, 1983 ; Tu et al., 2019 ; Weber and Harman, 2005 ).…”

Protocol for laser-induced chronic ocular hypertension and intracameral injection in nonhuman primates

“… If the IOP is not consistently increased (>21 mmHg), repeated photocoagulation is required at intervals of three weeks. Note: The baseline IOP of rhesus monkeys is similar to that of humans ( Lin et al., 2021 ; Pasquale et al., 2021 ; Quigley and Hohman, 1983 ; Tu et al., 2019a , Tu et al., 2019b ). It is generally necessary to perform 2–4 laser photocoagulation sessions.…”

“…Note: The baseline IOP of rhesus monkeys is similar to that of humans ( Lin et al., 2021 ; Pasquale et al., 2021 ; Quigley and Hohman, 1983 ; Tu et al., 2019a , Tu et al., 2019b ).…”