Abstract
Purpose: :
Development of a behavioral test using an obstacle course for evaluation of achromatopsia-affected dogs.
Methods: :
A 12 x 4 ft obstacle course was constructed with 47.5" tall, white PVC panels. Panels were set in moveable tracks spaced at varying intervals along the course. Dogs age 11 weeks to 1.5 years, were tested at four ambient light intensities (0.02, 2.3, 6 and 60 ft-c), 3 trials per dog. New combinations of panel positions were selected for each trial; 5 normal (carrier) and 5 achromatopsia-affected dogs (CNGB3 mutants) were evaluated. Visual status was masked to the test operators. All trials were recorded on DVD and times measured off-line. Time required to complete the course was compared between groups with univariate and multivariate analyses. In addition, preliminary trials were conducted with 2 achromatopsia dogs following recombinant adeno-associated virus-mediated gene replacement therapy.
Results: :
Once dogs were socialized, they were readily tested without previous course training. The mean (SE) time to complete the course at 0.02 ft-c was 4.4s (0.29) for carrier and 4.2s (0.26) for affected dogs (p=0.78). At 60 ft-c, the carrier dogs mean (SE) time was 4.5s (0.27) and the affected dogs was 25.5s (3.64). Significant time increases were measured at all light intensities greater than 2.3ft-c (p<0.0003) but no significant differences in performance were measured at 0.02ft-c (p=0.78) between groups. These statistical significance differences are maintained after adjustment by age, gender and trial. Preliminary results in the treated dogs confirmed successful outcome of gene therapy.
Conclusions: :
Our obstacle course provides an objective behavioral test for evaluating dogs with visual impairments such as achromatopsia at different ambient light intensities. It holds promise as an additional tool for evaluating the outcomes of new therapies.
Keywords: photoreceptors: visual performance • gene transfer/gene therapy • degenerations/dystrophies