Iqcb1 And Pde6b Mutations Cause Similar Early Onset Retinal Degenerations In Two Closely Related Terrier Dog Breeds, Orly Goldstein, Jason G. Mezey, Peter A. Schweitzer, A. Boyko, Chuan Gao, Carlos D. Bustamante, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland
Sep 2013
Iqcb1 And Pde6b Mutations Cause Similar Early Onset Retinal Degenerations In Two Closely Related Terrier Dog Breeds, Orly Goldstein, Jason G. Mezey, Peter A. Schweitzer, A. Boyko, Chuan Gao, Carlos D. Bustamante, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
Purpose.: To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively.
Methods.: Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the “MAGIC” genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease.
Results.: Structural photoreceptor abnormalities were observed in crd1 …
Transient Photoreceptor Deconstruction By Cntf Enhances Raav-Mediated Cone Functional Rescue In Late Stage Cngb3-Achromatopsia, Andras Komaromy, Jessica S. Rowlan, Amanda T. Parton Corr, Shelby L. Reinstein, Sanford L. Boye, Ann E. Cooper, Amaliris Gonzalez, Britt Levy, Rong Wen, William W. Hauswirth, William A. Beltran, Gustavo D. Aguirre
May 2013
Transient Photoreceptor Deconstruction By Cntf Enhances Raav-Mediated Cone Functional Rescue In Late Stage Cngb3-Achromatopsia, Andras Komaromy, Jessica S. Rowlan, Amanda T. Parton Corr, Shelby L. Reinstein, Sanford L. Boye, Ann E. Cooper, Amaliris Gonzalez, Britt Levy, Rong Wen, William W. Hauswirth, William A. Beltran, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Achromatopsia is a genetic disorder of cones, and one of the most common forms is a channelopathy caused by mutations in the β-subunit, CNGB3, of the cone cyclic nucleotide-gated (CNG) channel. Recombinant adeno-associated virus of serotype 5 (rAAV5)-mediated gene transfer of human CNGB3 cDNA to mutant dog cones results in functional and structural rescue in dogs <0.5 years of age, but treatment is minimally effective in dogs >1 year. We now test a new therapeutic concept by combining gene therapy with the administration of ciliary neurotrophic factor (CNTF). Intravitreal CNTF causes transient dedifferentiation of photoreceptors, a process called deconstruction, whereby …
Exclusion Of Rpgrip1 Ins44 From Primary Causal Association With Early-Onset Cone–Rod Dystrophy In Dogs, Tatyana Kuznetsova, Simone Iwabe, Kathleen Boesze-Battaglia, Sue Pearce-Kelling, Yim Chang-Min, Kendra Mcdaid, Keiko Miyadera, Andras Komaromy, Gustavo D. Aguirre
Jul 2012
Exclusion Of Rpgrip1 Ins44 From Primary Causal Association With Early-Onset Cone–Rod Dystrophy In Dogs, Tatyana Kuznetsova, Simone Iwabe, Kathleen Boesze-Battaglia, Sue Pearce-Kelling, Yim Chang-Min, Kendra Mcdaid, Keiko Miyadera, Andras Komaromy, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose.: Canine cone–rod dystrophy 1 (cord1) has been previously mapped to CFA15, and a homozygous 44-bp insertion in exon 2 (Ins44) of canine RPGRIP1(cRPGRIP1Ins/Ins ) has been associated with the disease. However, from the recent identification of a significant discordance in genotype–phenotype association, we have reexamined the role of cRPGRIP1 in cord1.
Methods.: Retinal structure and function was assessed by clinical retinal examination, noninvasive imaging, electroretinography, and histopathology/immunohistochemistry. cRPGRIP1 splicing was analyzed by RT-PCR. Retinal gene expression was determined by quantitative RT-PCR (qRT-PCR). Five markers spanning the entire cRPGRIP1 were identified and used for haplotyping. …
Gene Therapy Rescues Cone Function In Congenital Achromatopsia, Andras Komaromy, John J. Alexander, Jessica S. Rowlan, Monique M. Garcia, Vincent Chiodo, Asli Kaya, Jacqueline C. Tanaka, Gregory M. Acland, William W. Hauswirth, Gustavo D. Aguirre
Dec 2009
Gene Therapy Rescues Cone Function In Congenital Achromatopsia, Andras Komaromy, John J. Alexander, Jessica S. Rowlan, Monique M. Garcia, Vincent Chiodo, Asli Kaya, Jacqueline C. Tanaka, Gregory M. Acland, William W. Hauswirth, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
The successful restoration of visual function with recombinant adeno-associated virus (rAAV)-mediated gene replacement therapy in animals and humans with an inherited disease of the retinal pigment epithelium has ushered in a new era of retinal therapeutics. For many retinal disorders, however, targeting of therapeutic vectors to mutant rods and/or cones will be required. In this study, the primary cone photoreceptor disorder achromatopsia served as the ideal translational model to develop gene therapy directed to cone photoreceptors. We demonstrate that rAAV-mediated gene replacement therapy with different forms of the human red cone opsin promoter led to the restoration of cone function …
Development And Characterization Of A Normalized Canine Retinal Cdna Library For Genomic And Expression Studies, Barbara Zangerl, Qi Sun, Jarek Pillardy, Jennifer L. Johnson, Peter A. Schweitzer, Alvaro G. Hernandez, Lei Liu, Gregory M. Acland, Gustavo D. Aguirre
May 2006
Development And Characterization Of A Normalized Canine Retinal Cdna Library For Genomic And Expression Studies, Barbara Zangerl, Qi Sun, Jarek Pillardy, Jennifer L. Johnson, Peter A. Schweitzer, Alvaro G. Hernandez, Lei Liu, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
purpose. Identification of causative mutations for retinal blinding disorders is often limited by restricted understanding of gene expression and underlying molecular mechanisms that trigger degenerative processes. This study was conducted to develop a catalog of canine retina-expressed genes that would provide a unique tool to investigate normal and altered function in the adult retina. Because of the conserved syntenies between the dog and human, this approach would identify new potential disease candidate genes for both species.
methods. A canine normalized retinal cDNA library was produced and analyzed by using a modified PhredPhrap algorithm. Computerized annotation provided gene homology and chromosomal location for …
A Frameshift Mutation In Rpgr Exon Orf15 Causes Photoreceptor Degeneration And Inner Retina Remodeling In A Model Of X-Linked Retinitis Pigmentosa, William A. Beltran, Pamela Hammond, Gregory M. Acland, Gustavo D. Aguirre
Mar 2006
A Frameshift Mutation In Rpgr Exon Orf15 Causes Photoreceptor Degeneration And Inner Retina Remodeling In A Model Of X-Linked Retinitis Pigmentosa, William A. Beltran, Pamela Hammond, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
purpose. To characterize the course of retinal disease in X-linked progressive retinal atrophy 2 (XLPRA2), a canine model of early onset X-linked retinitis pigmentosa (XLRP) caused by a two-nucleotide microdeletion in RPGR ORF15.
methods. The retinas of 25 XLPRA2-affected dogs (age range, 2–40.6 weeks) and age-matched control subjects were collected, fixed, and embedded in epoxy resin for morphologic evaluation or in optimal cutting temperature (OCT) medium for TUNEL assay and immunohistochemistry. Cell-specific antibodies were used to examine changes in rods and cones and to evaluate the effects of the primary photoreceptor degeneration on inner retinal cells.
results. Abnormal development of …
Linkage Mapping Of Canine Rod Cone Dysplasia Type 2 (Rcd2) To Cfa7, The Canine Orthologue Of Human 1q32, Anna Kukekova, Jacquelyn Nelson, R W. Kuchtey, Jennifer K. Lowe, Jennifer L. Johnson, Elaine A. Ostrander, Gustavo D. Aguirre, Gregory M. Acland
Feb 2006
Linkage Mapping Of Canine Rod Cone Dysplasia Type 2 (Rcd2) To Cfa7, The Canine Orthologue Of Human 1q32, Anna Kukekova, Jacquelyn Nelson, R W. Kuchtey, Jennifer K. Lowe, Jennifer L. Johnson, Elaine A. Ostrander, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
purpose. To map the canine rcd2 retinal degeneration locus. Rod–cone dysplasia type 2 (rcd2), an early-onset autosomal recessive form of progressive retinal atrophy (PRA), is phenotypically similar to early-onset forms of retinitis pigmentosa collectively termed Leber congenital amaurosis and segregates naturally in the collie breed of dog. Multiple genes have previously been evaluated as candidates for rcd2, but all have been excluded.
methods. A set of informative experimental pedigrees segregating the rcd2phenotype was produced. A genome-wide scan of these pedigrees using a set of 241 markers was undertaken. To refine the localized homology between canine and human maps, …
Two Forms Of The Large Tumor Suppressor Gene (Lats1) Protein Expressed In The Vertebrate Retina, Novrouz B. Akhmedov, Clyde K. Yamashita, Dai Tran, Natik I. Piri, Gustavo D. Aguirre, Debora B. Farber
Mar 2005
Two Forms Of The Large Tumor Suppressor Gene (Lats1) Protein Expressed In The Vertebrate Retina, Novrouz B. Akhmedov, Clyde K. Yamashita, Dai Tran, Natik I. Piri, Gustavo D. Aguirre, Debora B. Farber
Gustavo D. Aguirre, VMD, PhD
The large tumor suppressor gene (Lats1) encodes a protein kinase that is highly conserved from fly to human, and plays a crucial role in the prevention of tumor formation by controlling mitosis progression. We have found that in addition to the previously isolated 7.5 kb long form of Lats1 (Lats1L) mRNA, a less abundant, shorter, 3.4 kb primary transcript (Lats1S) also is expressed in the vertebrate retina. Compared toLats1L, the sequence of Lats1S mRNA has a deletion of exons 6, 7, and 8 that corresponds to 792 bp …
The Proto-Oncogene C-Kit Maps To Canid B-Chromosomes, Alexander S. Graphodatsky, Anna V. Kukekova, Dmitry V. Yudkin, Vladimir A. Trifonov, Nadezhda V. Vorobieva, Violetta R. Beklemisheva, Polina L. Perelman, Daria A. Graphodatskaya, Lyudmila N. Trut, Fengtang Yang, Malcolm A. Ferguson-Smith, Gregory M. Acland, Gustavo D. Aguirre
Jan 2005
The Proto-Oncogene C-Kit Maps To Canid B-Chromosomes, Alexander S. Graphodatsky, Anna V. Kukekova, Dmitry V. Yudkin, Vladimir A. Trifonov, Nadezhda V. Vorobieva, Violetta R. Beklemisheva, Polina L. Perelman, Daria A. Graphodatskaya, Lyudmila N. Trut, Fengtang Yang, Malcolm A. Ferguson-Smith, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Plant and animal karyotypes sometimes contain variable elements, that are referred to as additional or B-chromosomes. It is generally believed that B-chromosomes lack major genes and represent parasitic and selfish elements of a genome. Here we report, for the first time, the localization of a gene to B-chromosomes of mammals: red fox (Vulpes vulpes) and two subspecies of raccoon dog (Nyctereutes procyonoides). Identification of the proto-oncogene C-KIT on B-chromosomes of twoCanidae species that diverged from a common ancestor more than 12.5 million years ago argues against the current view of B-chromosomes. Analyses of fox B-chromosomal …
A Marker Set For Construction Of A Genetic Map Of The Silver Fox (Vulpes Vulpes), Anna V. Kukekova, Lyudmila N. Trut, Irina N. Oskina, Anastasiya V. Kharlamova, Svetlana G. Shikhevich, E F. Kirkness, Gustavo D. Aguirre, Gregory M. Acland
Dec 2003
A Marker Set For Construction Of A Genetic Map Of The Silver Fox (Vulpes Vulpes), Anna V. Kukekova, Lyudmila N. Trut, Irina N. Oskina, Anastasiya V. Kharlamova, Svetlana G. Shikhevich, E F. Kirkness, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
The silver fox, a variant of the red fox (Vulpes vulpes), is a close relative of the dog (Canis familiaris). Cytogenetic differences and similarities between these species are well understood, but their genomic organizations have not been compared at higher resolution. Differences in their behavior also remain unexplained. Two silver fox strains demonstrating markedly different behavior have been generated at the Institute of Cytology and Genetics of the Russian Academy of Sciences. Foxes selected for tameness are friendly, like domestic dogs, while foxes selected for aggression resist human contact. To refine our understanding of the comparative genomic organization of dogs …
Comparative Analysis And Expression Of Clul1, A Cone Photoreceptor-Specific Gene, Qi Zhang, William A. Beltran, Zuohua Mao, Kui Li, Jennifer L. Johnson, Gregory M. Acland, Gustavo D. Aguirre
Sep 2003
Comparative Analysis And Expression Of Clul1, A Cone Photoreceptor-Specific Gene, Qi Zhang, William A. Beltran, Zuohua Mao, Kui Li, Jennifer L. Johnson, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: To characterize CLUL1, a cone photoreceptor-specific gene.
Methods: A comparative genomics approach was used to analyze the gene organization and protein sequence of a retinal clusterin-like protein and to identify conserved elements between human and dog. Its expression was studied by Northern and Western analyses and its localization by in situ hybridization and immunocytochemistry.
Results: The CLUL1 sequences of the human and dog share 85% and 73% identity, respectively, at the nucleotide and deduced amino acid level. The gene is organized into nine exons and shows strong homology, not only in exonic but also in some intronic sequences between the species. …
Linkage Mapping Of The Primary Disease Locus For Collie Eye Anomaly, Jennifer Lowe, Anna Kukekova, Ewen Kirkness, Gustavo Aguirre, Mariela Langlois, Gregory Acland, Elaine Ostrander
Jun 2003
Linkage Mapping Of The Primary Disease Locus For Collie Eye Anomaly, Jennifer Lowe, Anna Kukekova, Ewen Kirkness, Gustavo Aguirre, Mariela Langlois, Gregory Acland, Elaine Ostrander
Gustavo D. Aguirre, VMD, PhD
Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary ceaphenotype, choroidal hypoplasia, segregates …
Radiation Hybrid Map, Physical Map, And Low-Pass Genomic Sequence Of The Canine Prcd Region On Cfa9 And Comparative Mapping With The Syntenic Region On Human Chromosome 17 ☆, Duska Sidjanin, B Miller, J. W. Kijas, J Mcelwee, Jarek Pillardy, J Malek, G Pai, Tamara Feldblyum, C Fraser, Gregory Acland, Gustavo Aguirre
Jan 2003
Radiation Hybrid Map, Physical Map, And Low-Pass Genomic Sequence Of The Canine Prcd Region On Cfa9 And Comparative Mapping With The Syntenic Region On Human Chromosome 17 ☆, Duska Sidjanin, B Miller, J. W. Kijas, J Mcelwee, Jarek Pillardy, J Malek, G Pai, Tamara Feldblyum, C Fraser, Gregory Acland, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Progressive rod–cone degeneration (prcd) is a canine retinal disease that maps to the centromeric end of CFA9 in a region of synteny with the distal part of HSA17q. As such,prcd has been postulated as the only animal model of RP17, a human retinitis pigmentosa locus that maps to 17q22. In an effort to establish more detailed regions of synteny between dog CFA9 and the HSA17q–ter region, we created a robust gene-enriched CFA9-RH083000 map with 34 gene-based markers and 12 microsatellites, with the highest resolution and number of markers for the centromeric end of CFA9. Furthermore, we …
Comparative Analysis, Gene Organization And Expression Of Canine Tcte1l, Kui Li, Qi Zhang, Jennifer L. Johnson, Gustavo D. Aguirre
Dec 2002
Comparative Analysis, Gene Organization And Expression Of Canine Tcte1l, Kui Li, Qi Zhang, Jennifer L. Johnson, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
The murine t-complex-associated testis-expressed 1-like gene (TCTE1L) of the dog was cloned, characterized, and compared to the human ortholog. The characterized region of cDNA includes 351 bp of coding sequence which encodes a protein of 116 amino acids. The canine gene, spanning about 8.5 kb sequence, consists of 5 exons, with the initiation and stop codons found in the first and last exons, respectively. The comparative analyses reveal the evolutionarily conserved exonic and intronic regions, as well as gene flanking sequences. A 2.1 kb transcript was ubiquitously expressed in all the tissues examined, and secondarily down-expressed in the …
Canine Models Of Ocular Disease: Outcross Breedings Define A Dominant Disorder Present In The English Mastiff And Bull Mastiff Dog Breeds, J. W. Kijas, B J. Miller, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Gregory M. Acland
Dec 2002
Canine Models Of Ocular Disease: Outcross Breedings Define A Dominant Disorder Present In The English Mastiff And Bull Mastiff Dog Breeds, J. W. Kijas, B J. Miller, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
Progressive retinal atrophies (PRA) are a heterogeneous group of inherited eye diseases common to both dogs and man. Over 100 individual canine breeds display some sort of retinal degeneration, making the dog an extremely valuable resource both for finding the genetic determinants of inherited blindness and for developing naturally occurring animal models that mimic human disease. Progressive retinal atrophies within the English mastiff displayed an ambiguous mode of inheritance. By conducting outcross matings between affected English mastiffs and normal animals from other breeds, the mode of inheritance was confirmed as dominant. This directed candidate gene analysis and led to identification …
Retinal Histopathology Of An Xlrp Carrier With A Mutation In The Rpgr Exon Orf15, Gustavo Aguirre, Beverly Yashar, Sinoj John, Julie Smith, K Breuer, S Hiriyanna, Anand Swaroop, Ann Milam
Sep 2002
Retinal Histopathology Of An Xlrp Carrier With A Mutation In The Rpgr Exon Orf15, Gustavo Aguirre, Beverly Yashar, Sinoj John, Julie Smith, K Breuer, S Hiriyanna, Anand Swaroop, Ann Milam
Gustavo D. Aguirre, VMD, PhD
X-linked retinitis pigmentosa comprises the severe forms of RP, with early onset of night blindness, rapid constriction of visual fields and eventual loss of central acuity. Of the five distinct XLRP loci identified on the X chromosome, mutations have been found only in theRP2 and RPGR genes. Of these, mutations in RPGR are more common, particularly in a mutational hot spot that was identified in the newly discovered exon ORF15. We report on an extended family with a microdeletion in RPGR exon ORF15 and the retinalhistopathology of a female carrier of this mutation. We found a 1 bp …
Encapsulated Cell-Based Delivery Of Cntf Reduces Photoreceptor Degeneration In Animal Models Of Retinitis Pigmentosa, Weng Tao, Rong Wen, Moses B. Goddard, Sandy D. Sherman, Pam J. O'Rourke, Paul F. Stabila, William J. Bell, Brenda J. Dean, Konrad A. Kauper, Veronica A. Budz, William G. Tsiaras, Gregory M. Acland, Sue Pearce-Kelling, Alan Laties, Gustavo D. Aguirre
Sep 2002
Encapsulated Cell-Based Delivery Of Cntf Reduces Photoreceptor Degeneration In Animal Models Of Retinitis Pigmentosa, Weng Tao, Rong Wen, Moses B. Goddard, Sandy D. Sherman, Pam J. O'Rourke, Paul F. Stabila, William J. Bell, Brenda J. Dean, Konrad A. Kauper, Veronica A. Budz, William G. Tsiaras, Gregory M. Acland, Sue Pearce-Kelling, Alan Laties, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: The objective of the present study was to evaluate the therapeutic efficacy of ciliary neurotrophic factor (CNTF) delivered through encapsulated cells directly into the vitreous of the eye in an rcd1 canine model of retinitis pigmentosa. The dose–range effect of the treatment was also investigated.
Methods: Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell-containing capsules were then surgically implanted into the vitreous of one eye of rcd1 dogs at 7 weeks of age, when retinal degeneration is in progress but not complete. The …
Canine Cngb3 Mutations Establish Cone Degeneration As Orthologous To The Human Achromatopsia Locus Achm3, Duska J. Sidjanin, Jennifer K. Lowe, John L. Mcelwee, Bruce S. Milne, Taryn M. Phippen, David R. Sargan, Gustavo D. Aguirre, Gregory M. Acland, Elaine A. Ostrander
Dec 2001
Canine Cngb3 Mutations Establish Cone Degeneration As Orthologous To The Human Achromatopsia Locus Achm3, Duska J. Sidjanin, Jennifer K. Lowe, John L. Mcelwee, Bruce S. Milne, Taryn M. Phippen, David R. Sargan, Gustavo D. Aguirre, Gregory M. Acland, Elaine A. Ostrander
Gustavo D. Aguirre, VMD, PhD
Cone degeneration (cd ) is an autosomal recessive canine disease that occurs naturally in the Alaskan Malamute and German Shorthaired Pointer breeds. It is phenotypically similar to human achromatopsia, a heterogeneous autosomal recessive disorder associated with three distinct loci. Both the canine disease and its human counterparts are characterized by day-blindness and absence of retinal cone function in adults. We report linkage of the canine cd locus to marker C29.002 on canine chromosome 29 at recombination fraction 𝛉=0.0 with a maximum LOD score of 24.68 in a series of informative outbred pedigrees derived from cd-affected Alaskan Malamutes. Conserved gene order …
Concentric Retinitis Pigmentosa: Clinicopathologic Correlations, Ann Milam, Elaine De Castro, Julie Smith, Wai-Xing Tang, Sinoj John, Michael Gorin, Edwin Stone, Gustavo Aguirre, Samuel Jacobson
Sep 2001
Concentric Retinitis Pigmentosa: Clinicopathologic Correlations, Ann Milam, Elaine De Castro, Julie Smith, Wai-Xing Tang, Sinoj John, Michael Gorin, Edwin Stone, Gustavo Aguirre, Samuel Jacobson
Gustavo D. Aguirre, VMD, PhD
Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central …
Fine Mapping Of Canine Xlpra Establishes Homology Of The Human And Canine Rp3 Intervals, Qi Zhang, Gregory M. Acland, Barbara Zangerl, J. L. Johnson, Zuohua Mao, Caroline Zeiss, Elaine A. Ostrander, Gustavo D. Aguirre
Sep 2001
Fine Mapping Of Canine Xlpra Establishes Homology Of The Human And Canine Rp3 Intervals, Qi Zhang, Gregory M. Acland, Barbara Zangerl, J. L. Johnson, Zuohua Mao, Caroline Zeiss, Elaine A. Ostrander, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: Canine X-linked progressive retinal atrophy (XLPRA) is a hereditary, progressive retinal degeneration that has been mapped previously to the canine X chromosome in a region flanked by the dystrophin (DMD) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes, and is tightly linked to the gene RPGR. The comparable region of the human X chromosome includes the disease locus for RP3, an X-linked form of retinitis pigmentosa, although the current canine disease interval is much larger.
Methods: To refine the map of the canine XLPRA disease interval, 11 X-linked markers were mapped, both meiotically, in two extensive …
Cloning Of Canine Γ-Tubulin (Tubg1) Cdna And Mapping To Cfa9, Duska J. Sidjanin, F Xue, J Mcelwee, Jennifer L. Johnson, C Holmgren, Cathryn S. Mellersh, Elaine A. Ostrander, Gregory M. Acland, Gustavo D. Aguirre
Sep 2001
Cloning Of Canine Γ-Tubulin (Tubg1) Cdna And Mapping To Cfa9, Duska J. Sidjanin, F Xue, J Mcelwee, Jennifer L. Johnson, C Holmgren, Cathryn S. Mellersh, Elaine A. Ostrander, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
Gene Therapy Restores Vision In A Canine Model Of Childhood Blindness, Gregory M. Acland, Gustavo D. Aguirre, Jharna Ray, Qi Zhang, Tomas S. Aleman, Artur V. Cideciyan, Susan E. Pearce-Kelling, Vibha Anand, Yong Zeng, Albert M. Maguire, Samuel G. Jacobson, William W. Hauswirth, Jean Bennett
Apr 2001
Gene Therapy Restores Vision In A Canine Model Of Childhood Blindness, Gregory M. Acland, Gustavo D. Aguirre, Jharna Ray, Qi Zhang, Tomas S. Aleman, Artur V. Cideciyan, Susan E. Pearce-Kelling, Vibha Anand, Yong Zeng, Albert M. Maguire, Samuel G. Jacobson, William W. Hauswirth, Jean Bennett
Gustavo D. Aguirre, VMD, PhD
The relationship between the neurosensory photoreceptors and the adjacent retinal pigment epithelium (RPE) controls not only normal retinal function, but also the pathogenesis of hereditary retinal degenerations. The molecular bases for both primary photoreceptor1 and RPE diseases2, 3, 4 that cause blindness have been identified. Gene therapy has been used successfully to slow degeneration in rodent models of primary photoreceptor diseases5, 6, but efficacy of gene therapy directed at photoreceptors and RPE in a large-animal model of human disease has not been reported. Here we study one of the most clinically severe retinal degenerations, Leber congenital amaurosis (LCA). LCA causes …
Evaluation Of Retinal Photoreceptors And Pigment Epithelium In A Female Carrier Of Choroideremia, Nasreen Syed, Julie E. Smith, Sinoj K. John, Miguel C. Seabra, Gustavo D. Aguirre, Ann H. Milam
Mar 2001
Evaluation Of Retinal Photoreceptors And Pigment Epithelium In A Female Carrier Of Choroideremia, Nasreen Syed, Julie E. Smith, Sinoj K. John, Miguel C. Seabra, Gustavo D. Aguirre, Ann H. Milam
Gustavo D. Aguirre, VMD, PhD
Purpose: To clarify the pathogenesis of choroideremia.
Study Design: Human tissue study.
Tissues: Eyes of an 88-year-old symptomatic female carrier of choroideremia (CHM) and six normal, age-matched donors.
Methods: The eyes were processed for histopathologic examination, including immunocytochemistry with an antibody against the CHM gene product, REP-1, and retinal cell-specific markers.
Results: The CHM carrier retina showed patchy degeneration, but the photoreceptor and retinal pigment epithelium (RPE) loss appeared to be independent. The choriocapillaris was normal except where retinal areas were severely degenerate. The CHM gene product, REP-1, was localized to the cytoplasm of rods but not cones.
Conclusions: It …
Adenoviral Vector-Mediated Ss-Glucuronidase Cdna Transfer To Treat Mps Vii Rpe In Vitro, Maria E. Verdugo, Virginia Scarpino, Phillipe Moullier, M Haskins, Gustavo D. Aguirre, Jharna Ray
Dec 2000
Adenoviral Vector-Mediated Ss-Glucuronidase Cdna Transfer To Treat Mps Vii Rpe In Vitro, Maria E. Verdugo, Virginia Scarpino, Phillipe Moullier, M Haskins, Gustavo D. Aguirre, Jharna Ray
Gustavo D. Aguirre, VMD, PhD
Purpose. To develop an effective therapy for treating glycosaminoglycan (GAG) storage in mucopolysaccharidosis VII (MPS VII) retinal pigment epithelium (RPE) in vitro using adenoviral vector mediated human ß-glucuronidase cDNA (Ad-GUSB) transfer. Methods. Ad-GUSB was used to infect RPE at confluency. The transduction condition was optimized varying time of infection and number of infectious particles. The ß-glucuronidase (GUSB) activity was measured in transduced cells and media using a fluorogenic substrate. The GAG profiles were examined by metabolically labeling RPE with 35 Na 2 SO 4. Results. Transduced RPE, irrespective of species or disease status, expressed a high level of ß-glucuronidase. The …
Correspondence, Gustavo D. Aguirre
Feb 2000
Correspondence, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
No abstract provided.
Molecular Cloning, Characterization And Expression Of A Novel Retinal Clusterin-Like Protein Cdna, Qi Zhang, Kunal Ray, Gregory M. Acland, Jill M. Czarnecki, Gustavo D. Aguirre
Jan 2000
Molecular Cloning, Characterization And Expression Of A Novel Retinal Clusterin-Like Protein Cdna, Qi Zhang, Kunal Ray, Gregory M. Acland, Jill M. Czarnecki, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
A novel gene expressed predominantly in retina, but detected at a conspicuously lower level in retina of canine progressive rod cone degeneration (prcd), has been identified by suppression subtractive hybridization and retinal cDNA library screening. The characterized region of cDNA of the novel gene includes 1017 nucleotides of coding sequence predicted to encode a protein of 338 amino acids (Mr 39 389), 791 nucleotides of 5′-untranslated region (UTR), and 300 nucleotides of 3′-UTR including the poly(A)+ tail. Multiple transcripts were detected in retina by Northern blot analysis, and a lower level of expression was observed in …
Evaluation Of Cgmp-Phosphodiesterase (Pde) Subunits For Causal Association With Rod–Cone Dysplasia 2 (Rcd2), A Canine Model Of Abnormal Retinal Cgmp Metabolism, Weiquan Wang, Gregory Acland, Kunal Ray, Gustavo Aguirre
Sep 1999
Evaluation Of Cgmp-Phosphodiesterase (Pde) Subunits For Causal Association With Rod–Cone Dysplasia 2 (Rcd2), A Canine Model Of Abnormal Retinal Cgmp Metabolism, Weiquan Wang, Gregory Acland, Kunal Ray, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Rod-cone dysplasia types 1 (rcd1; Irish setter) and 2 (rcd2; collie) in dogs are early onset forms of progressive retinal atrophy (PRA) which serve as models of retinitis pigmentosa(RP) in humans. As bothrcd1 and rcd2 result from abnormal retinal cGMP metabolism associated with a deficiency in cGMP-phosphodiesterase (PDE) activity, and a nonsense mutation in the PDE6B subunit gene has been shown to cause rcd1, the genes encoding the four subunits of the PDE complex (PDE6A, PDE6B, PDE6G and PDE6D) make compelling candidates for the rcd2 locus. We adopted diverse strategies to evaluate causal association of the four PDE subunit genes …
Synthesis And Release Of Docosahexaenoic Acid By The Rpe Cells Of Prcd-Affected Dogs, Huiming Chen, Jharna Ray, Virginia Scarpino, Gregory M. Acland, Gustavo D. Aguirre, Robert E. Anderson
Aug 1999
Synthesis And Release Of Docosahexaenoic Acid By The Rpe Cells Of Prcd-Affected Dogs, Huiming Chen, Jharna Ray, Virginia Scarpino, Gregory M. Acland, Gustavo D. Aguirre, Robert E. Anderson
Gustavo D. Aguirre, VMD, PhD
Purpose: Dogs affected with progressive rod-cone degeneration (prcd) have reduced levels of docosahexaenoic acid (DHA, 22:6n-3) in their plasma and rod photoreceptor outer segments (ROS). Dietary supplementation of DHA has failed to increase the ROS DHA levels to that of unaffected control dogs. The present study was undertaken to test the hypothesis that prcd-affected dogs have a reduced capacity for the synthesis and/or release of DHA in retinal pigment epithelial (RPE) cells.
Methods: RPE cells (first passage cultures) from prcd-affected and normal dogs were incubated with [3H]eicosapentaenoic acid (EPA, 20:5n-3) for 24 and 72 hours. After …
A Novel Retinal Degeneration Locus Identified By Linkage And Comparative Mapping Of Canine Early Retinal Degeneration, Gregory Acland, Kunal Ray, Cathryn Mellersh, Amelia Langston, Jasper Rine, Elaine Ostrander, Gustavo Aguirre
Jul 1999
A Novel Retinal Degeneration Locus Identified By Linkage And Comparative Mapping Of Canine Early Retinal Degeneration, Gregory Acland, Kunal Ray, Cathryn Mellersh, Amelia Langston, Jasper Rine, Elaine Ostrander, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Early retinal degeneration (erd) is an early onset progressive retinal atrophy, a hereditary canine retinal disease phenotypically similar to human retinitis pigmentosa (RP). In previous efforts to identify the erd locus, canine homologs of genes causally associated with RP in humans, such as opsin (RHO), the β-subunit gene for cyclic GMP phosphodiesterase (PDE6B), and RDS/peripherin, were excluded. A genome-wide screen was undertaken on canine families segregating the erd disease. Analysis of over 150 canine-specific markers has localized erd to a single linkage group comprising two previously identified canine linkage groups, 20 and 26, corresponding to canine radiation hybrid groups RH.34-a …
Photoreceptor Dysplasia (Pd) In Miniature Schnauzer Dogs: Evaluation Of Candidate Genes By Molecular Genetic Analysis, Qi Zhang, V J. Baldwin, Gregory M. Acland, C J. Parshall, J. Haskell, Gustavo D. Aguirre, Kunal Ray
Dec 1998
Photoreceptor Dysplasia (Pd) In Miniature Schnauzer Dogs: Evaluation Of Candidate Genes By Molecular Genetic Analysis, Qi Zhang, V J. Baldwin, Gregory M. Acland, C J. Parshall, J. Haskell, Gustavo D. Aguirre, Kunal Ray
Gustavo D. Aguirre, VMD, PhD
Photoreceptor dysplasia (pd) is one of a group of at least six distinct autosomal and one X-linked retinal disorders identified in dogs which are collectively known as progressive retinal atrophy (PRA). It is an early onset retinal disease identified in miniature schnauzer dogs, and pedigree analysis and breeding studies have established autosomal recessive inheritance of the disease. Using a gene-based approach, a number of retina-expressed genes, including some members of the phototransduction pathway, have been causally implicated in retinal diseases of humans and other animals. Here we examined seven such potential candidate genes (opsin, RDS/peripherin, ROM1, rod cGMP-gated cation channel …
