GUCY2D-Associated Retinopathy: A Comparative Study Between Humans and German Spitz Dogs

The anatomical and physiological similarities between human and canine eyes suggest that dogs may serve as a valuable model for studying retinopathies and developing future gene therapies. This study aims to evaluate the similarities and differences between humans with GUCY2D gene variants causing Leber's congenital amaurosis (LCA) and a group of German Spitz dogs with hereditary retinopathy due to variants in the same gene, to assess their potential as an animal model for gene therapy research. A review of medical records, genetic testing, and ophthalmological examinations was conducted, including data such as age, genotyping, fundus photography, visual acuity (VA), fundus autofluorescence, optical coherence tomography (OCT), and electroretinography (ERG). Both groups presented subtle fundus abnormalities and severely reduced or absent ERG responses. In humans, OCT scans revealed decreased retinal thickness and structural alterations in the outer retinal layers. Similarly, the affected dogs exhibited focal neurosensory retinal detachments. The German Spitz model with GUCY2D variants shows significant parallels in retinal structure and functional impairment and may represent a promising candidate for preclinical gene therapy studies for LCA.