GENE THERAPY TO PROVIDE ROD FUNCTION IN CNGB1-/- DOGS WITH ESTABLISHED ROD LOSS.

Lauren E Kustasz won best oral presentation given by a veterinary student at our school's annual Phi Zeta Research day for her summer research project.  Check out her interesting work below, and congratulations to her on her Cases/Abstracts Award!

GENE THERAPY TO PROVIDE ROD FUNCTION IN CNGB1-/- DOGS WITH ESTABLISHED ROD LOSS.

Lauren E Kustasz-1, Laurence M Occelli-1,2, Paige A Winkler-1,2, Simon M Petersen-Jones-1,2

1) College of Veterinary Medicine, 2) Department of Small Animal Clinical Sciences, Michigan State University.

Progressive Retinal Atrophy (PRA) is a genetically heterogeneous hereditary disease that causes photoreceptor degeneration in dogs and is equivalent to Retinitis Pigmentosa in humans. The phenotype and mechanism as well as potential therapies have been studied in a colony of dogs with autosomal recessive PRA due to a mutation in Cngb1. In this disease, prior to rod death, there is a shortening of rod outer segments and deterioration of the photoreceptors as early as 8 weeks of age. We hypothesize that there is a stage during retinal degeneration after which gene therapy will no longer be able to rescue rod function or prevent rod cell death. The objectives of this study were to determine the success of gene supplementation in Cngb1-/- dogs and to assess the stage of retinal degeneration at which gene therapy can still restore useful visual function. Five Cngb1-/- dogs with different degrees of rod degeneration and loss (ages range from 3 to 10.5 months) were injected with the same AAV5 GRK1-cCNGB1 vector. The degree of restoration of rod function was assessed by electroretinography (ERG) and vision testing. The thickness and morphology of the photoreceptor layers was assessed using Spectral Domain-Optical Coherence Tomography in vivo. We found that dogs injected at 3, 5 and 6 months of age showed a larger improvement of rod-mediated ERG amplitudes and improved vision rescue in low light intensities compared to the dog treated at 10.5 months. This study shows that although successful in providing rod function, gene therapy is more effective in Cngb1-/- dogs with earlier stages of rod photoreceptor loss.