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Full-Text Articles in Medicine and Health Sciences
Modeling The Structural Consequences Of Best1 Missense Mutations, Karina E. Guziewicz, Gustavo D. Aguirre, Barbara Zangerl
Modeling The Structural Consequences Of Best1 Missense Mutations, Karina E. Guziewicz, Gustavo D. Aguirre, Barbara Zangerl
Gustavo D. Aguirre, VMD, PhD
Mutations in the bestrophin-1 gene (BEST1) are an important cause of inherited retinal disorders. Hitherto, over 100 unique allelic variants have been linked to the human BEST1 (hBEST1), and associated with disease phenotypes, broadly termed as bestrophinopathies. A spontaneous animal model recapitulating BEST1-related phenotypes, canine multifocal retinopathy (cmr), is caused by mutations in the canine gene ortholog (cBEST1). We have recently characterized molecular consequences of cmr, demonstrating defective protein trafficking as a result of G161D (cmr2) mutation. To further investigate the pathological effects of BEST1 missense mutations, canine and human peptide fragments derived from the protein sequence have been studied …
Recombinant Aav-Mediated Best1 Transfer To The Retinal Pigment Epithelium: Analysis Of Serotype-Dependent Retinal Effects, Karina E. Guziewicz, Barbara Zangerl, András M. Komáromy, Simone Iwabe, Vincent A. Chiodo, Sanford L. Boye, William W. Hauswirth, William Beltran, Gustavo D. Aguirre
Recombinant Aav-Mediated Best1 Transfer To The Retinal Pigment Epithelium: Analysis Of Serotype-Dependent Retinal Effects, Karina E. Guziewicz, Barbara Zangerl, András M. Komáromy, Simone Iwabe, Vincent A. Chiodo, Sanford L. Boye, William W. Hauswirth, William Beltran, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Mutations in the BEST1 gene constitute an underlying cause of juvenile macular dystrophies, a group of retinal disorders commonly referred to as bestrophinopathies and usually diagnosed in early childhood or adolescence. The disease primarily affects macular and paramacular regions of the eye leading to major declines in central vision later in life. Currently, there is no cure or surgical management for BEST1-associated disorders. The recently characterized human disease counterpart, canine multifocal retinopathy (cmr), recapitulates a full spectrum of clinical and molecular features observed in human bestrophinopathies and offers a valuable model system for development and testing of therapeutic strategies. In …
Canine Multifocal Retinopathy In The Australian Shepherd: A Case Report, Ingo Hoffmann, Karina E. Guziewicz, Barbara Zangerl, Gustavo D. Aguirre, Christian Y. Mardin
Canine Multifocal Retinopathy In The Australian Shepherd: A Case Report, Ingo Hoffmann, Karina E. Guziewicz, Barbara Zangerl, Gustavo D. Aguirre, Christian Y. Mardin
Gustavo D. Aguirre, VMD, PhD
A 1-year-old Australian Shepherd (AS) was presented for a routine hereditary eye examination. During the examination multiple raised, brown to orange lesions were noted in the fundus, which could not be attributed to a known retinal disease in this breed. As they clinically most closely resembled canine multifocal retinopathy (cmr) and no indication of an acquired condition was found, genetic tests for BEST1 gene mutations were performed. These showed the dog to be homozygous for the cmr1 (C73T/R25X) gene defect. Furthermore, ultrasound (US), electroretinography (ERG), and optical coherence tomography were performed, confirming changes typical for cmr. Subsequently, the AS pedigree …