Abstract
Purpose :
Preclinical safety assessment of pharmaceuticals using St. Kitts-origin African green monkeys (AGM; Chlorocebus sabeus) has expanded. Reference data on this species, however, are less extensive than for macaques. Here we present validated reference values for baseline intraocular pressure (IOP) in adult AGM (2014-2023, Males: n=138 eyes, Females: n=192 eyes).
Methods :
Ketamine/xylazine-sedated animals underwent baseline morning (8-10 am) IOP measurements using a Tonovet rebound tonometer (iCare, Finland) (n=330 eyes). A subset of animals of both sexes (M:4 eyes, F:2 eyes) underwent additional repetitive daily sedation (up to 6 days) to determine circadian and sedation influences on IOP. Additionally, different animals (M:40 eyes) underwent 0, 12, 16, 20 and 24 h measurements. Finally, latanoprost was administered topically in a different animal cohort with IOP measurements at baseline and 6 h post-treatment.
Results :
Mean IOP was 19.4±3.6 mmHg in males and 17.0±3.3 mmHg in females (mean±SD; p<0.0001), not secondary to differences in central corneal thickness. Measurements over the 6-day interval revealed an oscillatory pattern, with mean peak of 25.2 mmHg (Day 1) and 23.5 mmHg (Day 4), and low of 19.8 mmHg on both Day 3 and Day 5. Repetitive measurements over 24 h were characterized by a slight increase from 18.3 mmHg (baseline) to 19.1 mmHg at 24 h. Topical latanoprost decreased mean IOP by 3.4 mmHg in 66% of the animals (‘responders’) 6 h post-dosing. In ketamine/xylazine-sedated Cynomolgus monkeys (Macaca fasicularis; Lee HS, Lab Anim Res, 2021), time-dependent reductions in IOP were measured (TonoVet) in both sexes (14.7±3.7 at 5 min; 11.6±3.0 mmHg at 40 min). Cynomolgus males (n=5) exhibited significantly higher IOPs than females (n=5) over this 40-minute window.
Conclusions :
The AGM, a well-established NHP accepted by regulatory agencies for bridging and IND-enabling studies, shares many similarities to the macaque. Herein, we document that this is true for resting IOP, under sedation, with AGMs exhibiting similar sexual dimorphism, but greater stability in IOP during sedation. In addition, we document daily variations in IOP, and sensitivity to latanoprost in two-thirds of AGMs.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.