Purpose: The aim of study was to establish Rdh12 -associated inherited retinal disease (Rdh12 -IRD) mouse model and to identify the best timepoint for gene therapy.
Methods: We induced retinal degeneration in Rdh12 ^−/− mice using a bright light. We clarified the establishment of Rdh12 -IRD mouse model by analyzing the thickness of retinal layers and electroretinography (ERG). Rdh12 -IRD mice received a subretinal injection of adeno-associated virus 2/8-packaged Rdh12  cDNA for treatment. We evaluated the visual function and retinal structure in the treated and untreated eyes to identify the best timepoint for gene therapy.
Results: Rdh12 -IRD mice showed significant differences in ERG amplitudes and photoreceptor survival compared to Rdh12 ^+/+ mice. Preventive gene therapy not only maintained normal visual function but also prevented photoreceptor loss. Salvage gene therapy could not reverse the retinal degeneration phenotype of Rdh12 -IRD mice, but it could slow down the loss of visual function.
Conclusion: The light-induced retinal degeneration in our Rdh12 ^−/− mice indicated that a defect in Rdh12  alone was sufficient to cause visual dysfunction and photoreceptor degeneration, which reproduced the phenotypes observed in RDH12 -IRD patients. This model is suitable for gene therapy studies. Early treatment of the primary Rdh12  defect helps to delay the later onset of photoreceptor degeneration and maintains visual function in Rdh12 -IRD mice.
Keywords: Rdh12 , retinal diseases, mouse model, gene therapy