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Articles 1 - 30 of 70
Full-Text Articles in Medicine and Health Sciences
Raav2/5 Gene-Targeting To Rods: Dose-Dependent Efficiency And Complications Associated With Different Promoters, William Beltran, Sanford L. Boye, Shannon E. Boye, Vince A. Chiodo, Alfred S. Lewin, William W. Hauswirth, Gustavo D. Aguirre
Raav2/5 Gene-Targeting To Rods: Dose-Dependent Efficiency And Complications Associated With Different Promoters, William Beltran, Sanford L. Boye, Shannon E. Boye, Vince A. Chiodo, Alfred S. Lewin, William W. Hauswirth, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
A prerequisite for using corrective gene therapy to treat humans with inherited retinal degenerative diseases that primarily affect rods is to develop viral vectors that target specifically this population of photoreceptors. The delivery of a viral vector with photoreceptor tropism coupled with a rod-specific promoter is likely to be the safest and most efficient approach to target expression of the therapeutic gene to rods. Three promoters that included a fragment of the proximal mouse opsin promoter (mOP), the human G-protein-coupled receptor protein kinase 1 promoter (hGRK1), or the cytomegalovirus immediate early enhancer combined with the chicken β actin proximal promoter …
Window Into Retinal Studies, Gustavo D. Aguirre
Window Into Retinal Studies, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Professor Gustavo Aguirre discusses the context of his research studies at the University of Pennsylvania, which are currently concentrating on the degenerative disease, retinitis pigmentosa.
Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna V. Kukekova, Gustavo D. Aguirre, Gregory M. Acland
Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna V. Kukekova, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
Fine mapping followed by candidate gene analysis of erd — a canine hereditary retinal degeneration characterized by aberrant photoreceptor development — established that the disease cosegregates with a SINE insertion in exon 4 of the canine STK38L/NDR2 gene. The mutation removes exon 4 from STK38L transcripts and is predicted to remove much of the N terminus from the translated protein, including binding sites for S100B and Mob proteins, part of the protein kinase domain, and a Thr-75 residue critical for autophosphorylation. Although known to have roles in neuronal cell function, the STK38L pathway has not previously been implicated in normal …
Photoreceptor Dysplasia: An Inherited Progressive Retinal Atrophy Of Miniature Schnauzer Dogs, Charles J. Parshall, Milton Wyman, Susan Nitroy, Gregory M. Acland, Gustavo D. Aguirre
Photoreceptor Dysplasia: An Inherited Progressive Retinal Atrophy Of Miniature Schnauzer Dogs, Charles J. Parshall, Milton Wyman, Susan Nitroy, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
A progressive retinal atrophy (PRA) affecting Miniature Schnauzer dogs is reported. Of the 287 individuals (148 female, 139 male) comprising the study population, 66 (23 percent) were affected (33 female, 33 male) and 221 animals (115 female, 106 male) were phenotypically normal. There was no sex predilection for the disease. Results of histologic and electroretinographic studies indicate that the disease is a new and different type of PRA, characterized by unique morphologic and functional deficits during rod and cone development. Accordingly, the disease has been termed photoreceptor dysplasia. Clinically, and particularly ophthalmoscopically, diagnosis is only practicable in very late stages …
Drug Delivery To Posterior Intraocular Tissues: Third Annual Arvo/Pfizer Ophthalmics Research Institute Conference, Henry F. Edelhauser, Jeffrey H. Boatright, John M. Nickerson, Gustavo D. Aguirre
Drug Delivery To Posterior Intraocular Tissues: Third Annual Arvo/Pfizer Ophthalmics Research Institute Conference, Henry F. Edelhauser, Jeffrey H. Boatright, John M. Nickerson, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
The third Annual ARVO/Pfizer Ophthalmic Research Institute Conference was held Friday and Saturday, May 4 and 5, 2007 at the Fort Lauderdale Grande Hotel and Yacht Club, Fort Lauderdale, Florida. The conference, funded by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to develop strategies to address drug delivery to posterior intraocular tissues—a topic of great interest, as the major route of drug delivery is via intravitreous injection.
Identification Of Genetic Variation And Haplotype Structure Of The Canine Abca4 Gene For Retinal Disease Association Studies, Barbara Zangerl, Sarah J. Lindauer, Gregory M. Acland, Gustavo D. Aguirre
Identification Of Genetic Variation And Haplotype Structure Of The Canine Abca4 Gene For Retinal Disease Association Studies, Barbara Zangerl, Sarah J. Lindauer, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Over 200 mutations in the retina specific member of the ATP-binding cassette transporter superfamily (ABCA4) have been associated with a diverse group of human retinal diseases. The disease mechanisms, and genotype–phenotype associations, nonetheless, remain elusive in many cases. As orthologous genes are commonly mutated in canine models of human blinding disorders, canine ABCA4 appears to be an ideal candidate gene to identify and study sequence changes in dogs affected by various forms of inherited retinal degeneration. However, the size of the gene and lack of haplotype assignment significantly limit targeted association and/or linkage approaches. This study assessed the naturally observed …
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 …
Posterior Lenticonus In The Dog, Gustavo D. Aguirre, Stephen I. Bistner
Posterior Lenticonus In The Dog, Gustavo D. Aguirre, Stephen I. Bistner
Gustavo D. Aguirre, VMD, PhD
Posterior lenticonus is a congenital defect of the posterior lenticular surface. The posterior cortical and capsular regions of the lens have a circumscribed conelike or globular protrusion of variable size. Opacities may be present in the region of the conus. The defect has been reported in man, rabbits, calves and mice. This report documents 2 cases in unrelated dogs. The possible mechanism for the formation of this defect is discussed.
Posterior Segment Approach For Subretinal Transplantation Or Injection In The Canine Model, Maria E. Verdugo, Julie Alling, Eliot Lazar, Manuel Del Cerro, Jharna Ray, Gustavo D. Aguirre
Posterior Segment Approach For Subretinal Transplantation Or Injection In The Canine Model, Maria E. Verdugo, Julie Alling, Eliot Lazar, Manuel Del Cerro, Jharna Ray, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
A posterior segment approach for cell transplantation or injection into the subretinal space of the dog has been developed. Controlled penetration to the subretinal space was achieved using a 29-gauge injection cannula, either blunted or with a 30° sharpened bevel, and partially ensheathed with moveable plastic tubing. Depending on the injection volume used, the retina detached, and the fluid was reabsorbed within 1–3 weeks, although for smaller volumes the retina reattached within a matter of days. The optimal injection volume used was between 100 and 150 μl, or two injections of 55 μl each. By ophthalmoscopy following the surgery, it …
The Pathology Of The Feline Model Of Mucopolysaccharidosis I, Mark E. Haskins, Gustavo D. Aguirre, Peter F. Jezyk, Robert J. Desnick, Donald F. Patterson
The Pathology Of The Feline Model Of Mucopolysaccharidosis I, Mark E. Haskins, Gustavo D. Aguirre, Peter F. Jezyk, Robert J. Desnick, Donald F. Patterson
Gustavo D. Aguirre, VMD, PhD
Five cats with feline α-L-iduronidase-deficient mucopolysaccharidosis were studied. Membrane-bound cytoplasmic inclusions were present in central nervous system neurons, hepatocytes, chondrocytes, vascular and splenic smooth muscle cells, bone marrow leukocytes, and fibroblasts of the skin, eye, and cardiac valves. The lesions in these cats closely resemble those described in human patients with mucopolysaccharidosis I H (Hurler syndrome).
Safety In Nonhuman Primates Of Ocular Aav2-Rpe65, A Candidate Treatment For Blindness In Leber Congenital Amaurosis, Samuel G. Jacobson, Sanford L. Boye, Tomas S. Aleman, Thomas J. Conlon, Caroline J. Zeiss, Alejandro J. Roman, Artur V. Cideciyan, Sharon B. Schwartz, András M. Komáromy, Michelle Doobrajh, Andy Y. Cheung, Alexandar Sumaroka, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Shalesh Kaushal, Albert M. Maguire, Terence R. Flotte, William W. Hauswirth
Safety In Nonhuman Primates Of Ocular Aav2-Rpe65, A Candidate Treatment For Blindness In Leber Congenital Amaurosis, Samuel G. Jacobson, Sanford L. Boye, Tomas S. Aleman, Thomas J. Conlon, Caroline J. Zeiss, Alejandro J. Roman, Artur V. Cideciyan, Sharon B. Schwartz, András M. Komáromy, Michelle Doobrajh, Andy Y. Cheung, Alexandar Sumaroka, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Shalesh Kaushal, Albert M. Maguire, Terence R. Flotte, William W. Hauswirth
Gustavo D. Aguirre, VMD, PhD
Leber congenital amaurosis (LCA) is a molecularly heterogeneous disease group that leads to blindness. LCA caused by RPE65 mutations has been studied in animal models and vision has been restored by subretinal delivery of AAV- RPE65 vector. Human ocular gene transfer trials are being considered. Our safety studies of subretinal AAV-2/2. RPE65 in RPE65 -mutant dogs showed evidence of modest photoreceptor loss in the injection region in some animals at higher vector doses. We now test the hypothesis that there can be vector-related toxicity to the normal monkey, with its human-like retina. Good Laboratory Practice safety studies following single intraocular …
Photoreceptor Cell Death, Proliferation And Formation Of Hybrid Rod/S-Cone Photoreceptors In The Degenerating Stk38l Mutant Retina, Ágnes I. Berta, Kathleen Boesze-Battaglia, Sem Genini, Orly Goldstein, Paul J. O'Brien, Ágoston Szél, Gregory M. Acland, William Beltran, Gustavo D. Aguirre
Photoreceptor Cell Death, Proliferation And Formation Of Hybrid Rod/S-Cone Photoreceptors In The Degenerating Stk38l Mutant Retina, Ágnes I. Berta, Kathleen Boesze-Battaglia, Sem Genini, Orly Goldstein, Paul J. O'Brien, Ágoston Szél, Gregory M. Acland, William Beltran, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
A homozygous mutation in STK38L in dogs impairs the late phase of photoreceptor development, and is followed by photoreceptor cell death (TUNEL) and proliferation (PCNA, PHH3) events that occur independently in different cells between 7–14 weeks of age. During this period, the outer nuclear layer (ONL) cell number is unchanged. The dividing cells are of photoreceptor origin, have rod opsin labeling, and do not label with markers specific for macrophages/microglia (CD18) or Müller cells (glutamine synthetase, PAX6). Nestin labeling is absent from the ONL although it labels the peripheral retina and ciliary marginal zone equally in normals and mutants. Cell …
The Briard Problem, Ronald C. Riis, Gustavo D. Aguirre
The Briard Problem, Ronald C. Riis, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
The Briard breed has stimulated some ophthalmic interest in Canada, Europe, and the United States. Ophthalmoscopic changes similar to central progressive retinal atrophy have been diagnosed. This report adds further insight into the type of retinal degeneration and questions the associated physical findings as they may relate to the retinal disease.
Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András M. Komáromy, John J. Alexander, Anne E. Cooper, Vince A. Chodo, Gregory M. Acland, William W. Hauswirth, Gustavo D. Aguirre
Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András M. Komáromy, John J. Alexander, Anne E. Cooper, Vince A. Chodo, Gregory M. Acland, William W. Hauswirth, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and specific expression of GFP …
Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair R. Philip, Sarah J. P Lindauer, Susan E. Pearce-Kelling, Roberts F. Mullins, Alexander S. Graphodatsky, Daniel Ripoll, Jeanette S. Felix, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre
Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair R. Philip, Sarah J. P Lindauer, Susan E. Pearce-Kelling, Roberts F. Mullins, Alexander S. Graphodatsky, Daniel Ripoll, Jeanette S. Felix, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Progressive rod–cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease-relevant interval was reduced to a 106-kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease-relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human, and mouse. The gene codes for a 54-amino-acid (aa) protein in dog and human and …
Sudden Acquired Retinal Degeneration In The Dog: Clinical And Morphologic Characterization Of The "Silent Retina" Syndrome, Gregory M. Acland, Nita L. Irby, Gustavo D. Aguirre, Stephen L. Gross, Susan F. Nitroy, Kathleen L. Notarfrancesco
Sudden Acquired Retinal Degeneration In The Dog: Clinical And Morphologic Characterization Of The "Silent Retina" Syndrome, Gregory M. Acland, Nita L. Irby, Gustavo D. Aguirre, Stephen L. Gross, Susan F. Nitroy, Kathleen L. Notarfrancesco
Gustavo D. Aguirre, VMD, PhD
Adult dogs occasionally become suddenly, totally and permanently blind. If examined soon after the onset of blindness, the dogs show no ophthalmologic evidence of disease sufficient to account for their problem and are usually in otherwise good health. The hallmark of this sudden, acquired retinal degeneration (SARD), that establishes it as a retinopathy, and distinguishes it from neurological disease, is the extinguished electroretinogram. The syndrome has been termed "Silent Retina Syndrome" and "Metabolic Toxic Retinopathy". Although uncommon, SARD has been diagnosed with increased frequency in recent years. Little retinal tissue has, however, become available for histopathologic characterization of the disease. …
Canine Retina Has A Primate Fovea-Like Bouquet Of Cone Photoreceptors Which Is Affected By Inherited Macular Degenerations, William Beltran, Artur V. Cideciyan, Karina E. Guziewicz, Simone Iwabe, Erin M. Scott, Svetlana V. Savina, Gordon Ruthel, Frank Stefano, Lingli Zhang, Richard Zorger, Alexander Sumaroka, Samuel G. Jacobson, Gustavo D. Aguirre
Canine Retina Has A Primate Fovea-Like Bouquet Of Cone Photoreceptors Which Is Affected By Inherited Macular Degenerations, William Beltran, Artur V. Cideciyan, Karina E. Guziewicz, Simone Iwabe, Erin M. Scott, Svetlana V. Savina, Gordon Ruthel, Frank Stefano, Lingli Zhang, Richard Zorger, Alexander Sumaroka, Samuel G. Jacobson, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal …
Assessment Of Canine Best1 Variations Identifies New Mutations And Establishes An Independent Bestrophinopathy Model (Cmr3), Barbara Zangerl, Kaisa Wickström, Julianna Slavik, Sarah J. Lindauer, Saija Ahonen, Claude Schelling, Hannes Lohi, Karina E. Guziewicz, Gustavo D. Aguirre
Assessment Of Canine Best1 Variations Identifies New Mutations And Establishes An Independent Bestrophinopathy Model (Cmr3), Barbara Zangerl, Kaisa Wickström, Julianna Slavik, Sarah J. Lindauer, Saija Ahonen, Claude Schelling, Hannes Lohi, Karina E. Guziewicz, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: Mutations in bestrophin 1 (BEST1) are associated with a group of retinal disorders known as bestrophinopathies in man and canine multifocal retinopathies (cmr) in the dog. To date, the dog is the only large animal model suitable for the complex characterization and in-depth studies of Best-related disorders. In the first report of cmr, the disease was described in a group of mastiff-related breeds (cmr1) and the Coton de Tulear (cmr2). Additional breeds, e.g., the Lapponian herder (LH) and others, subsequently were recognized with similar phenotypes, but linked loci are unknown. …
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
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 …
Comparative Genomic Mapping Of Uncharacterized Canine Retinal Ests To Identify Novel Candidate Genes For Hereditary Retinal Disorders, Barbara Zangerl, Jennifer L. Johnson, Jarek Pillardy, Qi Sun, Catherine André, Francis Galibert, Gregory M. Acland, Gustavo D. Aguirre
Comparative Genomic Mapping Of Uncharacterized Canine Retinal Ests To Identify Novel Candidate Genes For Hereditary Retinal Disorders, Barbara Zangerl, Jennifer L. Johnson, Jarek Pillardy, Qi Sun, Catherine André, Francis Galibert, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: To identify the genomic location of previously uncharacterized canine retina-expressed expressed sequence tags (ESTs), and thus identify potential candidate genes for heritable retinal disorders. Methods: A set of over 500 retinal canine ESTs were mapped onto the canine genome using the RHDF5000–2 radiation hybrid (RH) panel, and the resulting map positions were compared to their respective localization in the CanFam2 assembly of the canine genome sequence. Results: Unique map positions could be assigned for 99% of the mapped clones, of which only 29% showed significant homology to known RefSeq sequences. A comparison between RH map and sequence assembly indicated …
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
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. …
A Kutya Mint Modell Az Örökletes Retinadegenerációk Kutatásában / The Dog As A Model In Research Into Inherited Retinal Degenerations, Ágnes I. Berta, Ágoston Szél, Gustavo D. Aguirre
A Kutya Mint Modell Az Örökletes Retinadegenerációk Kutatásában / The Dog As A Model In Research Into Inherited Retinal Degenerations, Ágnes I. Berta, Ágoston Szél, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Összefoglalás: A kutya mint modellállat csak az elmúlt 15 évben került az érdeklődés középpontjába. A kutya retinája különösen érdekes, mivel számos örökletes retinadegeneráció szoros homológiát mutat az ember hasonló betegségeivel. Röviden összefoglaljuk a kutya retinájának sajátosságait és azokat az alapkutatásban használt módszereket, melyek segítségével a retina degenerációja leírható kutyában. A kutya örökletes retinadegenerációi közül a szemészek számára a legérdekesebb csoport a progresszív retinalis atrophia (PRA), mivel genetikai, patológiai és klinikai szempontból is nagyon hasonló a retinitis pigmentosa különböző típusaihoz. A PRA csoport tagjai élő modellrendszerek, melyek alkalmazhatók az örökletes retinadegenerációk alap- és klinikai kutatásában egyaránt. Ezekben a súlyos és mindenekelőtt …
Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre
Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. …
Bone Marrow Transplantation For Feline Mucopolysaccharidosis I, Norman Matthew Ellinwood, Marie-Anne Colle, Margaret A. Weil, Margret L. Casal, Charles H. Vite, Staci Wiemelt, Christopher W. Hasson, Thomas M. O'Malley, Xingxuan He, Ulana Prociuk, Lucie Verot, John R. Melniczek, Anne Lannon, Gustavo D. Aguirre, Van W. Knox, Sydney M. Evans, Marie T. Vanier, Edward H. Schuchman, Steven U. Walkley, Mark E. Haskins
Bone Marrow Transplantation For Feline Mucopolysaccharidosis I, Norman Matthew Ellinwood, Marie-Anne Colle, Margaret A. Weil, Margret L. Casal, Charles H. Vite, Staci Wiemelt, Christopher W. Hasson, Thomas M. O'Malley, Xingxuan He, Ulana Prociuk, Lucie Verot, John R. Melniczek, Anne Lannon, Gustavo D. Aguirre, Van W. Knox, Sydney M. Evans, Marie T. Vanier, Edward H. Schuchman, Steven U. Walkley, Mark E. Haskins
Gustavo D. Aguirre, VMD, PhD
Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107–1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13–37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to …
A Non-Stop S-Antigen Gene Mutation Is Associated With Late Onset Hereditary Retinal Degeneration In Dogs, Orly Goldstein, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland
A Non-Stop S-Antigen Gene Mutation Is Associated With Late Onset Hereditary Retinal Degeneration In Dogs, Orly Goldstein, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
Purpose: To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog. Methods: Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated. Results: The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on …
A Digital Atlas Of The Dog Brain, Ritobrato Datta, Jongho Lee, Jeffrey Duda, Brian B. Avants, Charles H. Vite, Ben Tseng, Jim C. Gee, Gustavo D. Aguirre, Geoffrey K. Aguirre
A Digital Atlas Of The Dog Brain, Ritobrato Datta, Jongho Lee, Jeffrey Duda, Brian B. Avants, Charles H. Vite, Ben Tseng, Jim C. Gee, Gustavo D. Aguirre, Geoffrey K. Aguirre
Gustavo D. Aguirre, VMD, PhD
There is a long history and a growing interest in the canine as a subject of study in neuroscience research and in translational neurology. In the last few years, anatomical and functional magnetic resonance imaging (MRI) studies of awake and anesthetized dogs have been reported. Such efforts can be enhanced by a population atlas of canine brain anatomy to implement group analyses. Here we present a canine brain atlas derived as the diffeomorphic average of a population of fifteen mesaticephalic dogs. The atlas includes: 1) A brain template derived from in-vivo, T1-weighted imaging at 1 mm isotropic resolution at 3 …
Cloning And Characterization Of The Canine Photoreceptor Specific Cone-Rod Homeobox (Crx) Gene And Evaluation As A Candidate For Early Onset Photoreceptor Diseases In The Dog, Novrouz B. Akhmedov, Victoria Baldwin, Barbara Zangerl, James K. Kijas, Linda S. Hunter, Katayoun D. Minoofar, Cathryn Mellersh, Elaine A. Ostrander, Gregory M. Acland, Debora B. Farber, Gustavo D. Aguirre
Cloning And Characterization Of The Canine Photoreceptor Specific Cone-Rod Homeobox (Crx) Gene And Evaluation As A Candidate For Early Onset Photoreceptor Diseases In The Dog, Novrouz B. Akhmedov, Victoria Baldwin, Barbara Zangerl, James K. Kijas, Linda S. Hunter, Katayoun D. Minoofar, Cathryn Mellersh, Elaine A. Ostrander, Gregory M. Acland, Debora B. Farber, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
PURPOSE: The cone-rod homeobox protein (CRX) is a member of the homeodomain-containing protein family expressed in the retinal photoreceptors and pinealocytes; it is involved in the regulation of the coordinate expression of multiple photoreceptor specific genes during retinal development. Mutations in the CRX gene are causally associated with retinal degeneration phenotypes in man. To clone the full length cDNA, characterize the genomic organization of canine CRX, map the gene in a radiation hybrid (RH) panel, and evaluate it as a candidate for canine inherited retinal degenerations. METHODS: cDNA representational difference analysis (RDA) was done using normal and cone degeneration (cd) …
Cloning And Characterization Of The Cdna Encoding The Α-Subunit Of Cgmp-Phosphodiesterase In Canine Retinal Rod Photoreceptor Cells, Weiquan Wang, Gregory M. Acland, Gustavo D. Aguirre, Kunal Ray
Cloning And Characterization Of The Cdna Encoding The Α-Subunit Of Cgmp-Phosphodiesterase In Canine Retinal Rod Photoreceptor Cells, Weiquan Wang, Gregory M. Acland, Gustavo D. Aguirre, Kunal Ray
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
An Electrophysiologic Approach For Early Diagnosis Of Progressive Retinal Atrophy In The Norwegian Elkhound, Gustavo D. Aguirre, Lionel F. Rubin
An Electrophysiologic Approach For Early Diagnosis Of Progressive Retinal Atrophy In The Norwegian Elkhound, Gustavo D. Aguirre, Lionel F. Rubin
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
Criteria For Development Of Animal Models Of Diseases Of The Eye, Gustavo D. Aguirre
Criteria For Development Of Animal Models Of Diseases Of The Eye, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
No abstract provided.