Canine Best disease as a translational model.

Area of Science:

• Ophthalmology
• Genetics
• Translational Medicine

Background:

• Canine BEST1 mutations cause retinal degeneration mimicking human Best Vitelliform Macular Dystrophy (BVMD).
• Understanding the RPE-photoreceptor interface pathology is crucial for developing effective BVMD treatments.

Purpose of the Study:

• To characterize the clinical and microanatomical features of canine BEST1 disease.
• To evaluate the efficacy of AAV-mediated gene therapy in a canine model of BVMD.

Main Methods:

• Ophthalmic examination, cSLO/sdOCT imaging, and retinal immunohistochemistry were used.
• AAV-mediated gene therapy delivered the BEST1 transgene to the retinal pigment epithelium (RPE).

Main Results:

• Canine bestrophinopathies exhibit underdeveloped RPE apical microvilli, leading to RPE-retinal separation and lesion progression.
• Gene therapy corrected microdetachments and reversed lesions in dogs treated at the pseudohypopyon stage.

Conclusions:

• Canine BEST1 disease models accurately reflect human BVMD pathology.
• The canine model is a valuable translational tool for developing gene therapies for BVMD.