Canine models of inherited retinal diseases: from neglect to well-recognized translational value.

Abstract

Large animal models of inherited retinal diseases, particularly dogs, have been extensively used over the past decades to study disease natural history and evaluate therapeutic interventions. Our group of investigators at the University of Pennsylvania, School of Veterinary Medicine, has played a pivotal role in characterizing several of these animal models, documenting the natural history of their diseases, developing gene therapies, and conducting proof-of-concept studies. Additionally, we have assessed the potential toxicity of these therapies for human clinical trials, contributing to the regulatory approval of voretigene neparvovec-rzyl (Luxturna^®) by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with confirmed biallelic mutation-associated retinal dystrophy. In this review, we aim to summarize the clinical features of a subset of these diseases and reflect on the challenges encountered in integrating canine models into the translational pipeline.