Open Access. Powered by Scholars. Published by Universities.®
- Institution
- Keyword
-
- Dog (7)
- Retina (6)
- Retinal degeneration (5)
- BEST1 (3)
- Canine (3)
-
- Canine multifocal retinopathy (3)
- Dogs (3)
- Genetic variation (3)
- Retinitis pigmentosa (3)
- Affected dog (2)
- Animal (2)
- Animal model (2)
- Cornea (2)
- Disease models (2)
- Genetic diversity (2)
- Genetic linkage (2)
- Genetic markers (2)
- Genetic predisposition to disease (2)
- Photoreceptor (2)
- Progressive retinal atrophy (2)
- Retinal cell biology (2)
- Subretinal injection (2)
- ABCA4 (1)
- Achromatopsia (1)
- Albino rodents (1)
- Alkali burn (1)
- Amino acid (1)
- Area centrailis (1)
- Arginine (1)
- Australian Shepherd (1)
- Publication Type
Articles 1 - 30 of 52
Full-Text Articles in Ophthalmology
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 …
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 …
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 …
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 …
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. …
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.
Application Of A New Subretinal Injection Device In The Dog, András M. Komáromy, Signe E. Varner, Eugene De Juan, Gregory M. Acland, Gustavo D. Aguirre
Application Of A New Subretinal Injection Device In The Dog, András M. Komáromy, Signe E. Varner, Eugene De Juan, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
The use of a new subretinal injection device (RetinaJect™ Subretinal Cannula, SurModics, Inc., Eden Prairie, MN) to access the subretinal space in the canine model was evaluated. Subretinal injections were performed in 33 mongrel dogs between 2 and 52 months of age (median = 9 months). In 5 normal dogs the injection of 150 μl saline or India ink occurred by using a conventional subretinal injection device (CSID) with a 30-gauge anterior chamber irrigating cannula. The sclera had to be surgically exposed and penetrated before the subretinal injection with the CSID could occur. After removing the CSID, the conjunctiva over …
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
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 …
Viral-Antibody Complexes In Canine Adenovirus Type I (Cav-1) Ocular Lesion: Leukocyte Chemotaxis And Enzyme Release, Leland E. Carmichael, B. L. Medic, Stephen I. Bistner, Gustavo D. Aguirre
Viral-Antibody Complexes In Canine Adenovirus Type I (Cav-1) Ocular Lesion: Leukocyte Chemotaxis And Enzyme Release, Leland E. Carmichael, B. L. Medic, Stephen I. Bistner, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Canine adenovirus-type 1 (CAV-1)-antibody complexes caused severe anterior uveitis with corneal edema ("blue eye") when injected into the anterior chamber of normal dogs. The response of the anterior uvea to such immune complexes (IC) was similar to the spontaneously occurring disease. In the presence of complement (C'), IC caused release of neutrophile chemotactic factors. Following phagocytosis of IC-C', leukocytes released lysosomal enzymes, as indicated by the presence of acid phosphatase in the surrounding medium. Membrane bound viral aggregates, presumably IC, were common in neutrophiles and in macrophages that had infiltrated the anterior chamber of opaque eyes that occurred after intravenous …
Up-Regulation Of Tumor Necrosis Factor Superfamily Genes In Early Phases Of Photoreceptor Degeneration, Sem Genini, William Beltran, Gustavo D. Aguirre
Up-Regulation Of Tumor Necrosis Factor Superfamily Genes In Early Phases Of Photoreceptor Degeneration, Sem Genini, William Beltran, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
We used quantitative real-time PCR to examine the expression of 112 genes related to retinal function and/or belonging to known pro-apoptotic, cell survival, and autophagy pathways during photoreceptor degeneration in three early-onset canine models of human photoreceptor degeneration, rod cone dysplasia 1 (rcd1), X-linked progressive retinal atrophy 2 (xlpra2), and early retinal degeneration (erd), caused respectively, by mutations in PDE6B, RPGRORF15, and STK38L. Notably, we found that expression and timing of differentially expressed (DE) genes correlated with the cell death kinetics. Gene expression profiles of rcd1 and xlpra2 were similar; however rcd1 was more severe as demonstrated by the results …
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 …
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
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 …
Radiation Hybrid Mapping Of Cataract Genes In The Dog, Linda S. Hunter, Duska J. Sidjanin, Jennifer L. Johnson, Barbara Zangerl, Francis Galibert, Catherine Andre, Ewen Kirkness, Elijah Talamas, Gregory M. Acland, Gustavo D. Aguirre
Radiation Hybrid Mapping Of Cataract Genes In The Dog, Linda S. Hunter, Duska J. Sidjanin, Jennifer L. Johnson, Barbara Zangerl, Francis Galibert, Catherine Andre, Ewen Kirkness, Elijah Talamas, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: To facilitate the molecular characterization of naturally occurring cataracts in dogs by providing the radiation hybrid location of 21 cataract-associated genes along with their closely associated polymorphic markers. These can be used for segregation testing of the candidate genes in canine cataract pedigrees. Methods: Twenty-one genes with known mutations causing hereditary cataracts in man and/or mouse were selected and mapped to canine chromosomes using a canine:hamster radiation hybrid RH5000 panel. Each cataract gene ortholog was mapped in relation to over 3,000 markers including microsatellites, ESTs, genes, and BAC clones. The resulting independently determined RH-map locations were compared with the …
Ocular Manifestations Of Selected Systemic Diseases, Gustavo D. Aguirre, Stephen L. Gross
Ocular Manifestations Of Selected Systemic Diseases, Gustavo D. Aguirre, Stephen L. Gross
Gustavo D. Aguirre, VMD, PhD
Systemic diseases can present ocular manifestations. In some cases, the ocular lesions are present along with other generalized lesions characteristic of the disease. In a few cases, however, only ocular lesions are present. The interpretation of these ophthalmologic findings, together with the generalized signs exhibited by the patient, are important in establishing a differential diagnosis and prognosis for the patient. This article reviews selected systemic diseases and their ocular manifestations. A more exhaustive review of the diseases has been already presented.
Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory M. Acland, Gustavo D. Aguirre
Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 μg of CNTF in the left eye. The right eye served as a control and was injected …
Linkage Disequilibrium Mapping In Domestic Dog Breeds Narrows The Progressive Rod-Cone Degeneration Interval And Identifies Ancestral Disease-Transmitting Chromosome, Orly Goldstein, Barbara Zangerl, Sue Pearce-Kelling, Duska J. Sidjanin, James W. Kijas, Jeanette Felix, Gregory M. Acland, Gustavo D. Aguirre
Linkage Disequilibrium Mapping In Domestic Dog Breeds Narrows The Progressive Rod-Cone Degeneration Interval And Identifies Ancestral Disease-Transmitting Chromosome, Orly Goldstein, Barbara Zangerl, Sue Pearce-Kelling, Duska J. Sidjanin, James W. Kijas, Jeanette Felix, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Canine progressive rod–cone degeneration (prcd) is a retinal disease previously mapped to a broad, gene-rich centromeric region of canine chromosome 9. As allelic disorders are present in multiple breeds, we used linkage disequilibrium (LD) to narrow the ∼6.4-Mb interval candidate region. Multiple dog breeds, each representing genetically isolated populations, were typed for SNPs and other polymorphisms identified from BACs. The candidate region was initially localized to a 1.5-Mb zero recombination interval between growth factor receptor-bound protein 2 (GRB2) and SEC14-like 1 (SEC14L). A fine-scale haplotype of the region was developed, which reduced the LD interval to 106 kb and identified …