Retinal defects in mice after Ivermectin treatment

Abstract

Purpose : Here we describe retrospective analysis of retinal development defects correlated with Ivermectin treatment in BXD18 and BXD33 strains of mice.
Ivermectin is an antiparasitic drug that is used in the veterinary industry in North America and used in humans in Africa and South America.
We hypothesize that before the blood/retina barrier is formed Ivermectin can disrupt retinal development. Some strains of mice may be more susceptible to these effects.

Methods : Our mouse colony was treated with food containing Ivermectin (12 ppm) for 9 weeks to eliminate fur mites. Ivermectin treatment included breeding pairs, pregnant females, females with litters, and weanlings through adults of assorted ages. Visual function was tested by electroretinogram (ERG) and retina structure by fundus imaging and spectral domain optical coherence tomography (SD-OCT).
Further morphological analysis was performed on strains that showed visual deficits using plastic sections.

Results : While Ivermectin treatment effectively eliminated fur mites, we noticed that two strains of mice, BXD18 and BXD33, showed suppressed ERG oscillations and b-wave amplitudes, which were otherwise normal in these strains without Ivermectin treatment. This effect on the retina was not completely penetrant, with great variability in littermates and even large differences in each eye from the same animal.
SD-OCT images from BXD18 mice showed mostly normal structure of the retina, even in eyes that had no b-wave response. OCT images from BXD33 eyes that had no b-wave response were much thinner and seemed to be missing layers. It was difficult from the SD-OCT images to determine which layers were absent.
Morphology from plastic sections from the affected eyes of BXD mice showed that these eyes lack bipolar cells. The outer plexiform layer was also absent and the inner plexiform layer was greatly thinned. There were normal numbers of photoreceptors (both rods and cones), amacrine cells, and retinal ganglion cells in these eyes.

Conclusions : In some strains of mice, Ivermectin treatment causes defects in bipolar cell development. Caution is urged when conducting Ivermectin treatment of pregnant female mice and lactating females with neonates. A prospective study of Ivermectin treatment is ongoing.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.