A Novel Form of Progressive Retinal Atrophy in Swedish Vallhund Dogs
Publication Date
September 08, 2014
Journal
PLOS ONE
Authors
Ann E. Cooper, Saija Ahonen, Jessica S. Rowlan, Alison Duncan, et al
Volume
9
Issue
9
Pages
e106610
DOI
https://dx.plos.org/10.1371/journal.pone.0106610
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0106610
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25198798
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157785
Europe PMC
http://europepmc.org/abstract/MED/25198798
Web of Science
000341304700034
Scopus
84910092402
Mendeley
http://www.mendeley.com/research/novel-form-progressive-retinal-atrophy-swedish-vallhund-dogs
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Mendeley | Further Information

{"title"=>"A novel form of progressive retinal atrophy in Swedish vallhund dogs", "type"=>"journal", "authors"=>[{"first_name"=>"Ann E.", "last_name"=>"Cooper", "scopus_author_id"=>"57189686396"}, {"first_name"=>"Saija", "last_name"=>"Ahonen", "scopus_author_id"=>"6603360752"}, {"first_name"=>"Jessica S.", "last_name"=>"Rowlan", "scopus_author_id"=>"57189651042"}, {"first_name"=>"Alison", "last_name"=>"Duncan", "scopus_author_id"=>"56414098500"}, {"first_name"=>"Eija H.", "last_name"=>"Seppälä", "scopus_author_id"=>"7005530191"}, {"first_name"=>"Pä Ivi", "last_name"=>"Vanhapelto", "scopus_author_id"=>"56414835600"}, {"first_name"=>"Hannes", "last_name"=>"Lohi", "scopus_author_id"=>"6602309083"}, {"first_name"=>"András M.", "last_name"=>"Komáromy", "scopus_author_id"=>"7004884732"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84910092402", "sgr"=>"84910092402", "pui"=>"600286567", "pmid"=>"25198798", "doi"=>"10.1371/journal.pone.0106610"}, "id"=>"66d1a48f-2ccc-3dbe-94a1-c9f80fb4b6da", "abstract"=>"Inherited retinal degenerations, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), represent leading causes of incurable blindness in humans. This is also true in dogs, where the term progressive retinal atrophy (PRA) is used to describe inherited photoreceptor degeneration resulting in progressive vision loss. Because of the similarities in ocular anatomy, including the presence of a cone photoreceptor-rich central retinal region, and the close genotype-phenotype correlation, canine models contribute significantly to the understanding of retinal disease mechanisms and the development of new therapies. The screening of the pure-bred dog population for new forms of PRA represents an important strategy to establish new large animal models. By examining 324 dogs of the Swedish vallhund breed in seven countries and across three continents, we were able to describe a new and unique form of PRA characterized by the multifocal appearance of red and brown discoloration of the tapetal fundus followed over time by thinning of the retina. We propose three stages of the disease based on the appearance of the ocular fundus and associated visual deficits. Electroretinography revealed a gradual loss of both rod and cone photoreceptor-mediated function in Stages 2 and 3 of the disease. In the few dogs that suffered from pronounced vision loss, night-blindness occurred first in late Stage 2, followed by decreased day-vision in Stage 3. Histologic examinations confirmed the loss of photoreceptor cells at Stage 3, which was associated with the accumulation of autofluorescent material in the adjacent retinal pigment epithelium. Pedigree analysis was suggestive of an autosomal-recessive mode of inheritance. Mutations in six known canine retinal degeneration genes as well as hypovitaminosis E were excluded as causes of the disease. The observed variability in the age of disease onset and rate of progression suggest the presence of genetic and/or environmental disease modifiers.", "link"=>"http://www.mendeley.com/research/novel-form-progressive-retinal-atrophy-swedish-vallhund-dogs", "reader_count"=>17, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>3, "Veterinary Science and Veterinary Medicine"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>5}}, "reader_count_by_country"=>{"Finland"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1667014"], "description"=>"<p>Swedish vallhund dogs that showed no progression to subsequent disease stages with repeated examination.</p>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165408, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0106610.t002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Swedish_vallhund_dogs_that_showed_no_progression_to_subsequent_disease_stages_with_repeated_examination_/1165408", "title"=>"Swedish vallhund dogs that showed no progression to subsequent disease stages with repeated examination.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-08 03:36:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1666979"], "description"=>"<p>Compared to the ERG recordings of a normal dog (top row) both rod- and cone-mediated retinal functions are clearly reduced at <i>Stage 2</i>. ERG amplitudes are further decreased at <i>Stage 3</i> (third row), especially rod-mediated responses, and may not even be recordable in some affected dogs (flat lines in fourth row).</p>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165388, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0106610.g003", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Standard_electroretinograms_ERGs_recorded_from_normal_and_affected_Swedish_vallhund_dogs_/1165388", "title"=>"Standard electroretinograms (ERGs) recorded from normal and affected Swedish vallhund dogs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-08 03:36:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1667017", "https://ndownloader.figshare.com/files/1667018", "https://ndownloader.figshare.com/files/1667020", "https://ndownloader.figshare.com/files/1667021"], "description"=>"<div><p>Inherited retinal degenerations, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), represent leading causes of incurable blindness in humans. This is also true in dogs, where the term <i>progressive retinal atrophy (PRA)</i> is used to describe inherited photoreceptor degeneration resulting in progressive vision loss. Because of the similarities in ocular anatomy, including the presence of a cone photoreceptor-rich central retinal region, and the close genotype-phenotype correlation, canine models contribute significantly to the understanding of retinal disease mechanisms and the development of new therapies. The screening of the pure-bred dog population for new forms of PRA represents an important strategy to establish new large animal models. By examining 324 dogs of the Swedish vallhund breed in seven countries and across three continents, we were able to describe a new and unique form of PRA characterized by the multifocal appearance of red and brown discoloration of the tapetal fundus followed over time by thinning of the retina. We propose three stages of the disease based on the appearance of the ocular fundus and associated visual deficits. Electroretinography revealed a gradual loss of both rod and cone photoreceptor-mediated function in <i>Stages 2</i> and <i>3</i> of the disease. In the few dogs that suffered from pronounced vision loss, night-blindness occurred first in late <i>Stage 2</i>, followed by decreased day-vision in <i>Stage 3</i>. Histologic examinations confirmed the loss of photoreceptor cells at <i>Stage 3</i>, which was associated with the accumulation of autofluorescent material in the adjacent retinal pigment epithelium. Pedigree analysis was suggestive of an autosomal-recessive mode of inheritance. Mutations in six known canine retinal degeneration genes as well as hypovitaminosis E were excluded as causes of the disease. The observed variability in the age of disease onset and rate of progression suggest the presence of genetic and/or environmental disease modifiers.</p></div>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165409, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0106610.s001", "https://dx.doi.org/10.1371/journal.pone.0106610.s002", "https://dx.doi.org/10.1371/journal.pone.0106610.s003", "https://dx.doi.org/10.1371/journal.pone.0106610.s004"], "stats"=>{"downloads"=>7, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Novel_Form_of_Progressive_Retinal_Atrophy_in_Swedish_Vallhund_Dogs_/1165409", "title"=>"A Novel Form of Progressive Retinal Atrophy in Swedish Vallhund Dogs", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-09-08 03:36:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1667011"], "description"=>"<p>This pedigree is composed of nearly 300 dogs, including 125 animals affected with the breed-specific retinopathy. Affected dogs listed in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106610#pone-0106610-t001\" target=\"_blank\">Tables 1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106610#pone-0106610-t002\" target=\"_blank\">2</a> are highlighted in yellow and green, respectively. Squares, males; circles, females; white symbols, unaffected; black symbols, retinopathy affected.</p>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165405, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0106610.g005", "stats"=>{"downloads"=>3, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Large_Swedish_vallhund_pedigree_/1165405", "title"=>"Large Swedish vallhund pedigree.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-08 03:36:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1666978"], "description"=>"<p>(A–C) Normal appearance of the ocular fundus with the colored tapetum lucidum (responsible for eye shine), the well developed retinal vasculature, and the optic nerve head (arrows). It is not unusual to see a thin halo of altered reflectivity or <i>conus papillaris</i> around the optic nerve head as seen in B and C. (D–F) <i>Stage 1</i> is characterized by multifocal red or brown discoloration of the tapetal fundus (arrows). (G–I) In <i>Stage 2</i>, the retina showed signs of degeneration, indicated by multifocal, geographic thinning (arrow heads), beginning in the periphery and spreading throughout the tapetal fundus. (J–L) <i>Stage 3</i> is defined by a more diffuse retinal thinning recognized by the large, bright (hyperreflective) regions affecting most of the tapetal fundus (arrow heads). The <i>conus papillaris</i> also appears wider in <i>Stage 3</i> (arrows).</p>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165387, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0106610.g002", "stats"=>{"downloads"=>8, "page_views"=>355, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_appearance_of_the_ocular_fundi_of_normal_and_affected_Swedish_vallhund_dogs_/1165387", "title"=>"Clinical appearance of the ocular fundi of normal and affected Swedish vallhund dogs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-08 03:36:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1667005"], "description"=>"<p>(A) High quality section through a wildtype canine retina shows the normal retinal layers and architecture. (B) Different regions of the same 15-year old Swedish vallhund retina with <i>Stage 3</i> disease. Small islands of relatively normal appearing retina (B1) are surrounded by severely degenerated retina characterized by the loss of photoreceptors and ONL thinning (B2). Retinal architecture is completely lost with end-stage disease and severe retinal degeneration (B3). (C) At the transition between relatively well preserved and completely absent (*) retinal architecture, loss of photoreceptors (cones are labeled red with hCAR antibody) is associated with accumulation of autofluorescent material (green) in the subretinal space and within the RPE (arrows). (D) Accumulation of autofluorescent material (green) within the RPE can also be seen in a well preserved region of a 13-year old <i>Stage-2</i> affected retina (arrow), possibly indicating that increased autofluorescence may precede loss of photoreceptors. Accumulation of autofluorescent material within the RPE (arrows) can also be seen with other forms of PRA (E, prcd) or with normal aging (F, 11-year old normal canine retina) but to a much lesser extent than in affected Swedish vallhund dogs. Staining: H&E (A and B) and fluorescent immunolabeling (C–F). Cell nuclei are shown in blue with DAPI (C–F); hCAR, human cone arrestin; AF, autofluorescence. Calibration bars: 20 µm. Layers of the retina: RPE, retinal pigment epithelium; PR, photoreceptors; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; NFL, nerve fiber layer.</p>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165401, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0106610.g004", "stats"=>{"downloads"=>1, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histologic_changes_associated_with_Swedish_vallhund_retinopathy_/1165401", "title"=>"Histologic changes associated with Swedish vallhund retinopathy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-08 03:36:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1666954"], "description"=>"<p>The Swedish vallhund is a spitz-type herding breed, recognized since the age of the Vikings (700–1000 A.D.). The breed standard includes erect ears and a medium-length, hard haircoat. Coat color is a sable pattern in grey, red or combinations thereof. Tail may be natural (long, stub or bob) or docked.</p>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165377, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0106610.g001", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Appearance_of_Swedish_vallhund_dogs_/1165377", "title"=>"Appearance of Swedish vallhund dogs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-08 03:36:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1667013"], "description"=>"<p>At the authors' discretion, selected examinations performed by other certified veterinary ophthalmologists were included in the data analysis in order to provide a more complete picture of disease progression.</p><p>Swedish vallhund dogs that showed progression with repeated examination.</p>", "links"=>[], "tags"=>["rp", "degeneration", "Progressive Retinal Atrophy", "amd", "pra", "Swedish Vallhund Dogs Inherited", "Stage 3. Histologic examinations", "vision loss", "Swedish vallhund breed"], "article_id"=>1165407, "categories"=>["Biological Sciences"], "users"=>["Ann E. Cooper", "Saija Ahonen", "Jessica S. Rowlan", "Alison Duncan", "Eija H. Seppälä", "Päivi Vanhapelto", "Hannes Lohi", "András M. Komáromy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0106610.t001", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Swedish_vallhund_dogs_that_showed_progression_with_repeated_examination_/1165407", "title"=>"Swedish vallhund dogs that showed progression with repeated examination.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-08 03:36:00"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Nutrition", "average_usage"=>[289]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[310]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}, {"subject_area"=>"/Medicine and health sciences/Ophthalmology", "average_usage"=>[259, 385]}]}
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