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Full-Text Articles in Medicine and Health Sciences

Canine Rd3 Mutation Establishes Rod-Cone Dysplasia Type 2 (Rcd2) As Ortholog Of Human And Murine Rd3, Anna V. Kukekova, Orly Goldstein, Jennifer L. Johnson, Malcolm A. Richardson, Susan E. Pearce-Kelling, Anand Swaroop, James S. Friedman, Gustavo D. Aguirre, Gregory M. Acland Feb 2016

Canine Rd3 Mutation Establishes Rod-Cone Dysplasia Type 2 (Rcd2) As Ortholog Of Human And Murine Rd3, Anna V. Kukekova, Orly Goldstein, Jennifer L. Johnson, Malcolm A. Richardson, Susan E. Pearce-Kelling, Anand Swaroop, James S. Friedman, Gustavo D. Aguirre, Gregory M. Acland

Gustavo D. Aguirre, VMD, PhD

Rod-cone dysplasia type 2 (rcd2) is an autosomal recessive disorder that segregates in collie dogs. Linkage disequilibrium and meiotic linkage mapping were combined to take advantage of population structure within this breed and to fine map rcd2 to a 230-kb candidate region that included the gene C1orf36 responsible for human and murine rd3, and within which all affected dogs were homozygous for one haplotype. In one of three identified canine retinal RD3 splice variants, an insertion was found that cosegregates with rcd2 and is predicted to alter the last 61 codons of the normal open reading frame and further extend …


Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre Feb 2016

Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. The T4R RHO mutant dog retina shows retinal degeneration with exposures to light comparable to those used in clinical eye examinations of patients. To define the molecular mechanisms of the degeneration, AP-1 DNA-binding activity, composition, posttranslational modification of the protein complex, and modulation of ERK/MAPK signaling pathways were examined in light-exposed mutant retinas. METHODS. Dark-adapted retinas were exposed to short-duration light flashes from a retinal camera used clinically for retinal photography and were collected at different time points after exposure. Electrophoretic mobility shift assay (EMSA), supershift EMSA, Western blot analysis, and immunocytochemistry were used to examine AP-1 signaling. RESULTS. …


Development And Validation Of A Canine-Specific Profiling Array To Examine Expression Of Pro-Apoptotic And Pro-Survival Genes In Retinal Degenerative Diseases, Sem Genini, William Beltran, Gustavo D. Aguirre Feb 2016

Development And Validation Of A Canine-Specific Profiling Array To Examine Expression Of Pro-Apoptotic And Pro-Survival Genes In Retinal Degenerative Diseases, Sem Genini, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

We developed an expression profiling array to examine pro-apoptotic and pro-survival genes in dog retinal degeneration models. Gene-specific canine TaqMan assays were developed and included in a custom real-time quantitative reverse transcription-PCR (qRT-PCR) array. Of the 96 selected genes, 93 belonged to known relevant pro-apoptotic and pro-survival pathways, and/or were positive controls expressed in retina, while three were housekeeping genes. Ingenuity Pathway Analysis (IPA) showed that the selected genes belonged to expected biological functions (cell death, cell-mediated immune response, cellular development, function, and maintenance) and pathways (death receptor signaling, apoptosis, TNFR1 signaling, and induction of apoptosis by HIV1). Validation of …


Steroids Do Not Prevent Photoreceptor Degeneration In The Light-Exposed T4r Rhodopsin Mutant Dog Retina Irrespective Of Ap-1 Inhibition, Danian Gu, William Beltran, Sue Pearce-Kelling, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre Feb 2016

Steroids Do Not Prevent Photoreceptor Degeneration In The Light-Exposed T4r Rhodopsin Mutant Dog Retina Irrespective Of Ap-1 Inhibition, Danian Gu, William Beltran, Sue Pearce-Kelling, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. AP-1 has been proposed as a key intermediate linking exposure to light and photoreceptor cell death in rodent light-damage models. Inhibition of AP-1 associated with steroid administration also prevents light damage. In this study the role of steroids in inhibiting AP-1 activation and/or in preventing photoreceptor degeneration was examined in the rhodopsin mutant dog model. METHODS. The dogs were dark adapted overnight, eyes dilated with mydriatics; the right eye was light occluded and the fundus of the left eye photographed (∼15–17 overlapping frames) with a fundus camera. For biochemical studies, the dogs remained in the dark for 1 to …


Age-Dependent Disease Expression Determines Remodeling Of The Retinal Mosaic In Carriers Of Rpgr Exon Orfn15 Mutations, William Beltran, Gregory M. Acland, Gustavo D. Aguirre Feb 2016

Age-Dependent Disease Expression Determines Remodeling Of The Retinal Mosaic In Carriers Of Rpgr Exon Orfn15 Mutations, William Beltran, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. To characterize the retinal histopathology in carriers of X-linked progressive retinal atrophy (XLPRA1 and XLPRA2), two canine models of X-linked retinitis pigmentosa caused, respectively, by a stop and a frameshift mutation in RPGRORF15. METHODS. Retinas of XLPRA2 and XLPRA1 carriers of different ages were processed for morphologic evaluation, TUNEL assay, and immunohistochemistry. Cell-specific markers were used to examine retinal remodeling events. RESULTS. A mosaic pattern composed of patches of diseased and normal retina was first detected in XLPRA2 carriers at 4.9 weeks of age. A peak of photoreceptor cell death led to focal rod loss; however, in these patches …


Blinded By The Light: Retinal Phototoxicity In The Context Of Safety Studies, Maria Cristina De Vera Mudry, Sven Kronenberg, Shun-Ichiro Komatsu, Gustavo D. Aguirre Feb 2016

Blinded By The Light: Retinal Phototoxicity In The Context Of Safety Studies, Maria Cristina De Vera Mudry, Sven Kronenberg, Shun-Ichiro Komatsu, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

No abstract provided.