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Veterinary Medicine

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Progressive retinal atrophy

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Photoreceptor Dysplasia: An Inherited Progressive Retinal Atrophy Of Miniature Schnauzer Dogs, Charles J. Parshall, Milton Wyman, Susan Nitroy, Gregory M. Acland, Gustavo D. Aguirre Feb 2016

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 …

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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 Feb 2016

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 …

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A Non-Stop S-Antigen Gene Mutation Is Associated With Late Onset Hereditary Retinal Degeneration In Dogs, Orly Goldstein, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland Feb 2016

A Non-Stop S-Antigen Gene Mutation Is Associated With Late Onset Hereditary Retinal Degeneration In Dogs, Orly Goldstein, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland

Gustavo D. Aguirre, VMD, PhD

Purpose: To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog. Methods: Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated. Results: The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on …

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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 …

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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 …

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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 …

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Canine Rod Photoreceptor Cgmp-Gated Channel Protein Α-Subunit: Studies On The Expression Of The Gene And Characterization Of The Cdna, Qi Zhang, Sue Pearce-Kelling, Gregory Acland, Gustavo Aguirre, Kunal Ray Jul 1997

Canine Rod Photoreceptor Cgmp-Gated Channel Protein Α-Subunit: Studies On The Expression Of The Gene And Characterization Of The Cdna, Qi Zhang, Sue Pearce-Kelling, Gregory Acland, Gustavo Aguirre, Kunal Ray

Gustavo D. Aguirre, VMD, PhD

Rod photoreceptor cyclic GMP gated-channel protein is a key component of the visual transduction cascade in the vertebrate retina. The protein is composed of at least two subunits (α and β). Mutations in the α-subunit (CNGC1) have been shown to cause retinitis pigmentosa (RP) in humans. Several heterogeneous canine retinal diseases, which are clinically similar to RP, are known collectively as progressive retinal atrophy (PRA) and occur in dogs in a breed-specific manner. For the purpose of examining CNGC1 gene as a candidate for PRA, we report here the characterization of canine CNGC1 cDNA, and examine the expression of the …

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Differential Expression Of Photoreceptor-Specific Proteins During Disease And Degeneration In The Progressive Rod-Cone Degeneration (Prcd) Retina, Kathryn Gropp, Jun Huang, Gustavo Aguirre May 1997

Differential Expression Of Photoreceptor-Specific Proteins During Disease And Degeneration In The Progressive Rod-Cone Degeneration (Prcd) Retina, Kathryn Gropp, Jun Huang, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Progressive rod-cone degeneration (prcd) is a late-onset hereditary retinal degeneration characterized by normal development of photoreceptors prior to degeneration and death of visual cells. We reported previously that expression of opsin mRNA and protein decreases prior to visual cell degeneration. To examine the specificity of this reduction, we have used immunocytochemistry to correlate photoreceptor-specific protein expression with visual cell disease progression. Eyes from light-adapted age-matched control andprcd-affected dogs were fixed in paraformaldehyde, embedded in diethylene glycol distearate (DGD) wax, and reacted with antibodies specific to interphotoreceptor retinoid-binding protein (IRBP), S-antigen, opsin, phosducin, γ-phosphodiesterase (γ-PDE), and β1-transducin. While IRBP expression did …

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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 …

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Decreased Opsin Mrna And Immunoreactivity In Progressive Rod-Cone Degeneration (Prcd): Cytochemical Studies Of Early Disease And Degeneration, Jun Huang, Marie-Françoise Chesselet, Gustavo Aguirre Dec 1993

Decreased Opsin Mrna And Immunoreactivity In Progressive Rod-Cone Degeneration (Prcd): Cytochemical Studies Of Early Disease And Degeneration, Jun Huang, Marie-Françoise Chesselet, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Opsin mRNA level and immunoreactivity were examined by in situ hybridization and immunocytochemistry in normal and progressive rod cone degeneration (prcd)-affected dogs. In situ hybridization used 35S- and/or 3 H-labeled bovine opsin cRNA probes; immunocytochemistry used six monoclonal mouse anti-bovine opsin antibodies (MAb1) that are specific to different regions of the N-terminal, loop v-vi and the C-terminal domains. Optimal labeling and histological resolution at the single cell level were achieved with semi-thin sections of DGD wax-embedded tissues; it was possible to correlate the cytochemical observations with the disease staging in topographically defined regions that exhibited different disease severity. In early …

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Segregation Distortion In Inheritance Of Progressive Rod Cone Degeneration (Prcd) In Miniature Poodle Dogs, Gregory M. Acland, Susan Halloran-Blanton, Joann A. Boughman, Gustavo D. Aguirre Feb 1990

Segregation Distortion In Inheritance Of Progressive Rod Cone Degeneration (Prcd) In Miniature Poodle Dogs, Gregory M. Acland, Susan Halloran-Blanton, Joann A. Boughman, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Segregation distortion was observed in inheritance of progressive rod–cone degeneration (prcd) in a colony of Miniature Poodle dogs. Breeding results, from both retrospective records and prospectively planned matings, were classified into five mating types: (1) affected to affected, (2) homozygous normal sire to any dam, (3) heterozygous to heterozygous, (4) heterozygous sire to affected dam, and (5) affected sire to heterozygous dam. For all but the last category, results were in accord with mendelian expectations for autosomal-recessive inheritance. However, litters of mating type 5 had fewer affected pups (20/77) than expected. The observed segregation ratio for this mating type (0.26) …

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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 …

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