Gene Therapy in a Large Animal Model of PDE6A-Retinitis Pigmentosa.

Despite mutations in the rod phosphodiesterase 6-alpha () gene being well-recognized as a cause of human retinitis pigmentosa, no definitive treatments have been developed to treat this blinding disease. We performed a trial of retinal gene augmentation in the mutant dog using delivery by capsid-mutant adeno-associated virus serotype 8, previously shown to have a rapid onset of transgene expression in the canine retina. Subretinal injections were performed in 10 dogs at 29-44 days of age, and electroretinography and vision testing were performed to assess functional outcome.

Isolation and cultivation of canine uveal melanocytes.

Objectives: To establish a method for isolation and culture of canine uveal melanocytes.

Animals Studied: Uveal explants from five mixed-breed dogs.

Procedures: Donor globes were dissected, and the anterior uvea removed.

Evaluation of lateral spread of transgene expression following subretinal AAV-mediated gene delivery in dogs.

Dog models with spontaneously occurring mutations in retinal dystrophy genes are an invaluable resource for preclinical development of retinal gene therapy. Adeno-associated virus (AAV) vectors have been most successful; to target the outer retina and RPE they are delivered by subretinal injection, causing a temporary retinal detachment with some potential for retinal morbidity. A recent reporter gene study using an AAV2/8 vector in dogs reported transgene expression beyond the boundary of the subretinal bleb.