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Barbara Zangerl, Andras M. Komaromy, Simone Iwabe, Artur V. Cideciyan, Tomas S. Aleman, Samuel G. Jacobson, Gustavo D. Aguirre, Karina E. Guziewicz; In Vivo Imaging of BEST1-Related Retinal Changes in the Canine Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2160.
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Mutations in the BEST1 gene cause human bestrophinopathies and canine multifocal retinopathy (cmr). Both disorders exhibit comparable clinical and molecular features, but details about the often variable onset and progression of disease are lacking and, to date, no treatment is available. We have previously applied in vivo imaging techniques to visualize early changes of disease in the retina/RPE of affected dogs. The study aimed to define the long term progression of individual lesions and provide a baseline for evaluation of gene replacement therapy.
The retina/RPE of dogs with an early stop mutation in the BEST1 gene (C73T/R25X) was monitored by routine ophthalmoscopy on a monthly basis. Once dogs exhibited clinical signs of cmr, high resolution images were captured every two to four months using confocal scanning laser ophthalmoscopy in autofluorescence mode and spectral domain optical coherence tomography (SD-OCT) with a RTVue-100 (Optovue Inc) or a Spectralis HRA/OCT (Heidelberg Engineering). The same imaging protocol is currently being applied to dogs treated by subretinal injection of AAV2 promoting expression of full length BEST1 gene.
Typically, cmr presented before 12 months of age as focal retinal detachments. Accumulation of autofluorescent subretinal material and/or RPE abnormalities was observed with some lesions. Natural history of cmr involved lesions that can fluctuate in size and number. Occasionally, spontaneous resolution of individual detachment was observed. Retinal degeneration was not detectable in studied animals as of 26 months of age.
Longitudinal imaging studies suggest that cmr triggers elevations of the retina that fluctuate and can result in accumulation of autofluorescent material. Ongoing studies defining the natural history of cmr lesions are being used to assess the potential of gene replacement therapy and its prospect as a treatment choice for BEST1-related disorders in dog and in patients.
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