Abstract
Purpose :
The minipig (MP) has become an accepted animal model for the evaluation of ocular toxicity based on structural and function similarity to humans particularly as the availability of nonhuman primates becomes limited. This study evaluated the ocular effects of a small peptide molecule (MW <5kDa) following two intravitreal (IVT) injections.
Methods :
Bilateral injections of 0 (vehicle), 200 or 300 µg/eye were given on Day 1 with a second, unilateral injection given on Day 60. Ocular effects were evaluated with IOP, OCT and fundus imaging, direct and indirect ophthalmoscopy and ERG. The MPs (3/timepoint) were sacrificed on Days 6, 14, 28 and 88 for ocular tissue distribution and histopathological examination.
Results :
Vitreal haze without the presence of inflammatory cells was observed at 300 µg/eye. Stable, multiple “black streaks” were observed mostly along the superior retinal vessels in the treated eyes at both doses and controls. OCT scans, fundus images and ophthalmological evaluations did not reveal any morphological changes. The black streaks were likely possible focal pigment deposition, typical for MPs. No drug-related IOP or ERG changes were noted throughout the study. Microscopic findings were limited to the presence of drug-related accumulation in the vitreous at all timepoints at 200 and 300 µg/eye with no adverse pathology. Potential vehicle-related microscopic findings were limited to minimal mononuclear cell infiltration in the vitreous at all timepoints. The drug was detected in the choroid, retina and vitreous humor of the left eye at both doses on Days 6, 14, 28 and 88; retinal levels on Day 88 <LLOQ across all dose groups. Vitreal levels were ~10-fold higher on Day 28 or 88 compared to retinal and choroidal levels.
Conclusions :
The results reveal the MP is an acceptable species for evaluation of the ocular effects of single and repeated IVT injection. The findings also demonstrate microscopic findings that were typical of a MP.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.