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 …
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. …
Exploring A Short-Wavelength Sensitive Cone Mechanism To Brightness And Discomfort Glare, David Glabe
Apr 2012
Exploring A Short-Wavelength Sensitive Cone Mechanism To Brightness And Discomfort Glare, David Glabe
David K Glabe
Yellow lenses have long been reported to alter visual perception, including subjective impressions of brightness and discomfort glare. To date, no consensus has been reached regarding the physiological mechanism behind this altered perception, although recent research suggests a possible short-wavelength sensitive cone (S-cone) mechanism. An experiment was conducted to test the hypothesis that S-cones are responsible for the perceived increase in brightness and decrease in discomfort glare perception when viewing through yellow lenses. Thirty participants were asked to use neutral density filters to match perception of brightness and discomfort glare through colored filters and with no filters in low and …
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 …
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. …
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 …
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 …
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 …
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 …
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 …
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 …
Timp-1 Expression Is Increased In X-Linked Progressive Retinal Atrophy Despite Its Exclusion As A Candidate Gene, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre, Kunal Ray
Dec 1998
Timp-1 Expression Is Increased In X-Linked Progressive Retinal Atrophy Despite Its Exclusion As A Candidate Gene, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre, Kunal Ray
Gustavo D. Aguirre, VMD, PhD
X-linked progressive retinal atrophy (XLPRA) is the only known natural animal model for X-linked retinitis pigmentosa (XLRP), a blinding disorder in man. The tissue inhibitor metalloproteinase 1 gene (TIMP-1), present in close proximity to one of the two XLRPloci, was tested as a candidate for XLPRA, by first characterizing the cDNA and gene from a normal dog. The cloned canine TIMP-1 cDNA is predicted to encode a protein of 207 amino acids with 66–83% identity in the deduced aa sequence with homologous mammalian genes. No sequence difference in the coding sequence of …
Canine Cone Transducin-Gamma Gene And Cone Degeneration In The Cd Dog, Gustavo D. Aguirre
Aug 1998
Canine Cone Transducin-Gamma Gene And Cone Degeneration In The Cd Dog, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: To characterize the cDNA and the organization of the gene encoding the cone-specific gamma subunit of transducin (Tgamma c) and to examine this gene as a candidate for the recessively inherited cone photoreceptor degeneration in the cd dog.
Methods: Canine Tgamma c cDNA was cloned and sequenced. Polymerase chain reaction (PCR) was used to define the Tgamma c gene structure, northern blot analysis to examine the level of expression of Tgamma c mRNA in control and cd-affected retinas, and immunocytochemistry to determine the presence and localization of Tgamma c in normal and cd retinas.
Results: Immunocytochemical results showed Tgamma …
Characterization Of Canine Photoreceptor Phosducin Cdna And Identification Of A Sequence Variant In Dogs With Photoreceptor Dysplasia, Qi Zhang, Gregory M. Acland, Charles J. Parhsall, Jeanette Haskell, Kunal Ray, Gustavo D. Aguirre
Jul 1998
Characterization Of Canine Photoreceptor Phosducin Cdna And Identification Of A Sequence Variant In Dogs With Photoreceptor Dysplasia, Qi Zhang, Gregory M. Acland, Charles J. Parhsall, Jeanette Haskell, Kunal Ray, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Photoreceptor dysplasia (pd) is an autosomal recessive disease of miniature schnauzer dogs causing retinal degeneration. The disease is a homologue of retinitis pigmentosa, a group of genetically heterogeneous diseases, causing blindness in humans. A subtraction library was prepared from retinas of pd affected and age-matched normal control dogs to isolate de novo candidate genes for further examination. From the subtraction library, cDNA for phosducin (PDC), a member of the phototransduction pathway, was isolated as a transcript expressed at a higher level in the affected retina. First, the normal canine PDC cDNA was characterized to evaluate the PDC gene …
Construction Of A Panel Of Canine–Rodent Hybrid Cell Lines For Use In Partitioning Of The Canine Genome, Amelia A. Langston, Cathryn S. Mellersh, Cassandra L. Neal, Kunal Ray, Gregory M. Acland, Mark Gibbs, Gustavo D. Aguirre, R.E. K. Fournier, Elaine A. Ostrander
Dec 1997
Construction Of A Panel Of Canine–Rodent Hybrid Cell Lines For Use In Partitioning Of The Canine Genome, Amelia A. Langston, Cathryn S. Mellersh, Cassandra L. Neal, Kunal Ray, Gregory M. Acland, Mark Gibbs, Gustavo D. Aguirre, R.E. K. Fournier, Elaine A. Ostrander
Gustavo D. Aguirre, VMD, PhD
We have constructed a collection of canine–rodent microcell hybrid cell lines by fusion of canine fibroblast microcell donors with immortalized rodent recipient cells. Characterization of the hybrid cell lines using a combination of fluorescencein situhybridization and PCR analysis of canine microsatellite repeat sequences allowed selection of a panel of hybrids in which most canine chromosomes are represented. Approximately 90% of genetic markers and genes that were tested could be assigned to 1 of 31 anonymous canine chromosome groups, based on common patterns of retention in the hybrid set. Many of these putative chromosome groups have now been validated …
Canine Rod Transducin A-1: Cloning Of The Cdna And Evaluation Of The Gene As A Candidate For Progressive Retinal Atrophy, Kunal Ray, Victoria J. Baldwin, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre
Dec 1996
Canine Rod Transducin A-1: Cloning Of The Cdna And Evaluation Of The Gene As A Candidate For Progressive Retinal Atrophy, Kunal Ray, Victoria J. Baldwin, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: Progressive retinal atrophy (PRA) represents a heterogeneous group of retinal dystrophies, distinct forms of which occur in different canine breeds. The present study was undertaken to evaluate the gene for the a-1 subunit of the rod specific G-protein transducin (GNAT1), a member of the phototransduction pathway, as a candidate for progressive rod cone degeneration (prcd) in poodles, early retinal degeneration (erd) in elkhounds, and rod cone dysplasia 2 (rcd 2) in collies.
Methods: Oligonucleotide primers were designed from the consensus region of known cDNA sequences for GNAT1 from other species. Canine GNAT1 cDNA was cloned and sequenced after reverse …
Nonallelism Of Erd And Prcd And Exclusion Of The Canine Rds/Peripherin Gene As A Candidate For Both Retinal Degeneration Loci., K Ray, Gregory M. Acland, Gustavo D. Aguirre
Mar 1996
Nonallelism Of Erd And Prcd And Exclusion Of The Canine Rds/Peripherin Gene As A Candidate For Both Retinal Degeneration Loci., K Ray, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: To determine whether early retinal degeneration (erd) and progressive rod cone degeneration (prcd), two canine hereditary retinal degenerations, are caused by allelic mutations; to determine the cDNA sequence of the canine RDS/peripherin homolog (CFRDSP); and to test whether mutations(s) in CFRDSP cause(s) either erd or prcd.
Methods: Three erd-affected dogs were crossbred to three prcd-affected dogs, and their progeny were tested by electroretinography and retinal morphology for evidence of retinal degeneration. Canine RDS/peripherin cDNA was cloned and sequenced after reverse-transcription-polymerase chain reaction (RT-PCR) of total retinal RNA. A set of overlapping fragments of CFRDSP cDNA amplified from normal and …
Diethylene Glycol Distearate (Dgd): A Versatile Embedding Medium For Retinal Cytochemistry, Jun C. Huang, Kristina Mieziewska, Nancy Philp, Theo Van Veen, Gustavo D. Aguirre
Apr 1993
Diethylene Glycol Distearate (Dgd): A Versatile Embedding Medium For Retinal Cytochemistry, Jun C. Huang, Kristina Mieziewska, Nancy Philp, Theo Van Veen, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Embedment in diethylene glycol distearate (DGD) was shown to be highly desirable and versatile for retinal cytochemical studies, including in situ hybridization, immuno- andlectin cytochemistry. This method allows for preservation of fine tissue detail as well as good reaction sensitivity. It appears to be more suitable than most other methods currently used for light microscopic retinal cytochemistry.
The Cone Matrix Sheath In The Normal And Diseased Retina: Cytochemical And Biochemical Studies Of Peanut Agglutinin-Binding Proteins In Cone And Rod-Cone Degeneration, Kenneth Long, Gustavo Aguirre
May 1991
The Cone Matrix Sheath In The Normal And Diseased Retina: Cytochemical And Biochemical Studies Of Peanut Agglutinin-Binding Proteins In Cone And Rod-Cone Degeneration, Kenneth Long, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
The fate of the cone-associated extracellular domain, or cone matrix sheath (CMS), was examined in two canine models of hereditary retinal degeneration. The diseases, which affect cones selectively (cd = cone degeneration), or rods and cones temporally (prcd = progressive rod-cone degeneration), were examined biochemically (SDS-PAGE/lectinblots) and cytochemically (light microscopy) using peanut agglutinin lectin (PNA) to selectively label this domain and associated structures. Most of the cones had disappeared in the adult cd retina. In the remaining cones, PNA labeled the ectopically located somata and the CMSs that were present around severely diseased ones. …
Glycosaminoglycan And Collagen Metabolism In Arylsulfatase B-Deficient Retinal Pigment Epithelium In Vitro, Gustavo D. Aguirre, Lawrence E. Stramm, W Li, M Haskins
May 1991
Glycosaminoglycan And Collagen Metabolism In Arylsulfatase B-Deficient Retinal Pigment Epithelium In Vitro, Gustavo D. Aguirre, Lawrence E. Stramm, W Li, M Haskins
Gustavo D. Aguirre, VMD, PhD
Regional differences in retinal pigment epithelial (RPE) cell glycosaminoglycan (GAG) and collagen metabolism were studied using cells obtained from normal cats and those with deficient activity of arylsulfatase B (ASB), a lysosomal enzyme involved in GAG catabolism. Control and ASB-deficient RPE cultures initiated from superior equatorial (superior) and inferior equatorial (inferior) regions of the eye were radiolabeled for 72 hr with 35SO4, and GAGs from the media and cell layers were analyzed separately. In ASB-deficient RPE, there was an accumulation of dermatan/chondroitin sulfate in the cell layer of cultures initiated from the superior region of the eye but not in …
Β-Glucuronidase Mediated Pathway Essential For Retinal Pigment Epithelial Degradation Of Glycosaminoglycans. Disease Expression And In Vitro Disease Correction Using Retroviral Mediated Cdna Transfer, Lawrence Stramm, John Wolfe, Edward Schuchman, Mark Haskins, Donald Patterson, Gustavo Aguirre
Apr 1990
Β-Glucuronidase Mediated Pathway Essential For Retinal Pigment Epithelial Degradation Of Glycosaminoglycans. Disease Expression And In Vitro Disease Correction Using Retroviral Mediated Cdna Transfer, Lawrence Stramm, John Wolfe, Edward Schuchman, Mark Haskins, Donald Patterson, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
A β-glucuronidase mediated pathway for the degradation of glycosaminoglycans is present in the retinal pigment epithelium. The pathway has been defined using ocular tissues and cultured cells from mutant animals having a recessively inherited deficiency of the lysosomal enzyme. In situ, storage products accumulate in secondary lysosomes of the retinal pigment epithelium, the cytoplasm fills with inclusions and the cells hypertrophy; severity of the disease increases with aging. Deficient activity of β-glucuronidase is present in primary and second passage cultures. Radiolabel studies with 35SO4 show a significant retention of cell layer label by mutant retinal pigment epithelial cells …
Metabolic Labeling Of Rod Outer Segment Phospholipids In Miniature Poodles With Progressive Rod-Cone Degeneration (Prcd), Mary Wetzel, Christian Fahlman, Paul O'Brien, Gustavo Aguirre
Dec 1989
Metabolic Labeling Of Rod Outer Segment Phospholipids In Miniature Poodles With Progressive Rod-Cone Degeneration (Prcd), Mary Wetzel, Christian Fahlman, Paul O'Brien, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
The recessive genetic defect in miniature poodles which results in progressive rod-cone degeneration (prcd) has been investigated in an attempt to determine the biochemical abnormality involved. In the present study, the rod outer segments of young prcd affected miniature poodles and normal dogs have been compared with respect to the incorporation of intravitreally injected [3H]palmitic acid, [14C]linolenic acid, and [14C]docosahexaenoic acid into neutral lipids and phospholipids as well as [3H]palmitate and [14C]leucine into rhodopsin. In addition, 3 mm trephined punches of retinas were incubated with [ …
Retinal Pigment Epithelial Glycosaminoglycan Metabolism: Intracellular Versus Extracellular Pathways. In Vitro Studies In Normal And Diseased Cells, Gustavo D. Aguirre, Lawrence E. Stramm, M Haskins
Sep 1989
Retinal Pigment Epithelial Glycosaminoglycan Metabolism: Intracellular Versus Extracellular Pathways. In Vitro Studies In Normal And Diseased Cells, Gustavo D. Aguirre, Lawrence E. Stramm, M Haskins
Gustavo D. Aguirre, VMD, PhD
The synthesis and turnover of glycosaminoglycans (GAGs) in different fractions of cultured feline retinal pigment epithelium (RPE) were characterized. In one method of fractionation, trypsin was used to separate the extracellular components (referred to as trypsin-soluble glycocalyx) from the intracellular components. As a second method, the basal extracellular matrix (basal ECM) was separated from the rest of the GAGs (cell-associated GAGs) by extracting the cell layer with NH4OH. The incorporation of 35SO4 into cetylpyridinium chloride-precipitable GAGs in the cell-associated and the intracellular fractions increased throughout the labeling period, while in the trypsin-soluble glycocalyx and the basal ECM incorporation approached a …
S-Antigen In A Hereditary Visual Cell Disease. Immunocytochemical And Immunological Studies, Gustavo D. Aguirre, K Long, N Philp, I Gery
Oct 1988
S-Antigen In A Hereditary Visual Cell Disease. Immunocytochemical And Immunological Studies, Gustavo D. Aguirre, K Long, N Philp, I Gery
Gustavo D. Aguirre, VMD, PhD
S-antigen is a photoreceptor-specific and potentially autoantigenic protein. Using light microscopic immunocytochemistry, the localization of S-antigen was studied in the retinas of normal dogs and Irish setters affected with rod-cone dysplasia, a hereditary retinal degeneration characterized by abnormal cGMP metabolism and arrested outer segment differentiation. Normal and affected dogs were also tested for the presence of humoral and cellular immunity to S-antigen. S-antigen was present in both rods and cones during inner and outer segment differentiation, but there was an apparent loss of immunoreactivity in cones as the retina matured. The developmental appearance and localization of S-antigen in affected retinas …
Arylsulfatase B Activity In Cultured Retinal Pigment Epithelium: Regional Studies In Feline Mucopolysaccharidosis Vi., Lawrence E. Stramm, R J. Desnick, M Haskins, Gustavo D. Aguirre
Jun 1986
Arylsulfatase B Activity In Cultured Retinal Pigment Epithelium: Regional Studies In Feline Mucopolysaccharidosis Vi., Lawrence E. Stramm, R J. Desnick, M Haskins, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Feline mucopolysaccharidosis VI (MPS VI) is a recessively inherited lysosomal storage disease resulting from a deficiency of arylsulfatase B (ASB). Previous histopathologic findings have indicated that the disease is expressed morphologically in non-pigmented retinal pigment epithelial cells (RPE) in the posterior pole and superior equatorial regions by the accumulation of vacuolated inclusions and eventual cellular hypertrophy, while pigmented regions in the periphery are minimally affected. To determine if the regional and age-dependent variations in disease severity result from differences in residual enzyme activity, primary cultures of feline MPS VI-affected RPE were initiated from defined regions of the eye and maintained …
Reductions In Taurine Secondary To Photoreceptor Loss In Irish Setters With Rod-Cone Dysplasia, Gustavo D. Aguirre, S Y. Schmidt
Apr 1985
Reductions In Taurine Secondary To Photoreceptor Loss In Irish Setters With Rod-Cone Dysplasia, Gustavo D. Aguirre, S Y. Schmidt
Gustavo D. Aguirre, VMD, PhD
These studies show that onset of photoreceptor cell degeneration preceded the loss of taurine in retinas of Irish setters with rod-cone dysplasia. The numbers of photoreceptor cell nuclei were within the normal adult range in affected setters at 10 through 26 days of age but declined rapidly between 26 and 45 days and more gradually thereafter; their numbers became reduced to 50% of normal at 45 days and then to 12-20% and 3-10% of normal at 192 and 346 days, respectively. Taurine concentrations increased within the photoreceptor cell layer during normal development to peak values (50 mM) at a time …
Disease Expression In Cultured Pigment Epithelium. Feline Mucopolysaccharidosis Vi., Lawrence E. Stramm, M Haskins, R J. Desnick, Gustavo D. Aguirre
Jan 1985
Disease Expression In Cultured Pigment Epithelium. Feline Mucopolysaccharidosis Vi., Lawrence E. Stramm, M Haskins, R J. Desnick, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Primary cultures of retinal pigment epithelial (RPE) cells from cats with mucopolysaccharidosis VI (MPS VI) have been initiated from mixed populations of cells (ie, derived from the entire eyecup and represented by both pigmented and nonpigmented RPE cells). The cells were enzymatically dissociated from the eyecup and seeded at 6 X 10(4) cells/cm2. Cells from normal and affected cats formed confluent monolayers of polygonal cells between 5-10 days in culture and maintained most of their in vivo morphologic characteristics. The only abnormality observed in the MPS VI-affected cultures was the accumulation of vacuolated intracytoplasmic inclusions; when numerous, these vacuoles caused …
Experimental Eye Research Volume 35, Issue 6, December 1982, Pages 625–642 Cover Image Retinal Degenerations In The Dog Iii Abnormal Cyclic Nucleotide Metabolism In Rod-Cone Dysplasia, Gustavo Aguirre, Debora Farber, Richard Lolley, Paul O'Brien, James Alligood, R Fletcher
Nov 1982
Experimental Eye Research Volume 35, Issue 6, December 1982, Pages 625–642 Cover Image Retinal Degenerations In The Dog Iii Abnormal Cyclic Nucleotide Metabolism In Rod-Cone Dysplasia, Gustavo Aguirre, Debora Farber, Richard Lolley, Paul O'Brien, James Alligood, R Fletcher
Gustavo D. Aguirre, VMD, PhD
In dogs bred to develop rod-cone dysplasia, retinal development is normal until 13 days of age.Afterwards, there is an arrest of visual cell differentiation. Rod inner segments remain diminutive and outer segments fail to elongate as in controls; the outer segments show lamellar disorientation and disorganization. Affected visual cells degenerate, but the degeneration process is more rapid and extensive for rods than cones.
Cyclic GMP levels become elevated in affected retinas early during the postnatal differentiation of visual cells; this elevation precedes any morphological evidence of photoreceptor disease. Retinal protein synthesis is normal during the time that retinal cGMP levels …
Pathogenesis Of Progressive Rod-Cone Degeneration In Miniature Poodles, Gustavo D. Aguirre, James P. Alligood, P O'Brien, N Buyukmihci
Oct 1982
Pathogenesis Of Progressive Rod-Cone Degeneration In Miniature Poodles, Gustavo D. Aguirre, James P. Alligood, P O'Brien, N Buyukmihci
Gustavo D. Aguirre, VMD, PhD
Visual cell pathologic changes and outer segment renewal were investigated in miniature poodles with progressive rod-cone degeneration. Early in this disease, visual cells in the posterior pole and equatorial regions show outer segment lamellar disorientation and vesicular profiles. Visual cells are normal in the periphery. Outer segment renewal determined after intravitreal injection of 3H-leucine was abnormally slower in affected animals than in controls. This renewal abnormality was similar in structurally normal and diseased photoreceptors, suggesting that the renewal defect is the earliest recognizable abnormality in the disease. The pigment epithelium was normal; the presence and density of pigment did not …
