Abstract
Purpose :
Identification of test item related ophthalmic findings in ocular toxicology studies requires a working knowledge of background findings commonly encountered. Rabbits are extensively used in ocular safety due to their economic value, availability, ease of handling and history of use in the evaluation of ocular safety. Further, they offer better anatomic and physiological similarities to humans over rodents. This study looks at the incidence of ocular background findings in New Zealand White (NZW) and Dutch Belted (DB) rabbits.
Methods :
Historical data was collected from pretreatment ophthalmic exams of NZW (n≥1000) and DB (n≥800) rabbits used in toxicology studies at Charles River, Senneville site from 2017 to 2023. Animals were between 3 and 6 months of age and supplied by Charles River St. Constant (NZW) or Envigo (NZW and DB). Ophthalmic examinations of male and female rabbits included slit lamp biomicroscopy and indirect ophthalmoscopy.
Results :
Lens findings had the highest occurrence in both rabbit strains, with a rate of 19.2% for NZW and 16.2% for DB. These included nuclear lens opacity (5.6% and 5.4%), posterior cortical opacity (1.8% and 0.49%) and prominent lens nucleus (1.1% and 4.7%). Corneal background findings (corneal dystrophy and deep stromal opacities) were also notable at 8.9% and 9.6%, and sometimes led to recommendation of placement in the control group. Pigmented DB rabbits displayed retinal/choroidal pigment irregularities (9.3%), while the NZW displayed choroidal variation (4.18%). Other findings such as persistent pupillary membrane, myelin variation, hyaloid remnant, and vitreous or retinal opacities were observed in less than 1% of cases.
Conclusions :
The most frequent ocular background findings in these populations of laboratory rabbits were noted at the level of the lens. Although not severe enough to exclude animals from a study, some were recommended to be placed in control groups. To accurately evaluate ocular toxicities in nonclinical studies, it is important to consider historical control data. This data provides insight into the expected variation of background ocular changes in experimental animals. Since such findings can vary depending on the animal supplier, the lot (batch of animals) examined, and the facility at which the examinations were conducted. Regular updates are essential to maintain the validity of historical control data and account for genetic drift over time.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.