Evaluation of the major histocompatibility complex (MHC) class II as a candidate for sudden acquired retinal degeneration syndrome (SARDS) in Dachshunds

Abstract

Objective: Sudden acquired retinal degeneration syndrome (SARDS) is one of the leading causes of acute blindness in dogs, with an unknown etiology and no effective treatment. Certain breeds such as Dachshunds are overrepresented among SARDS patients, and therefore the syndrome is suspected to have a genetic component. The objective of this study was to determine if a genetic locus associated with SARDS in Dachshunds could be identified using a genome-wide association study (GWAS). Procedures: Genome-wide association mapping was performed in 15 SARDS-affected and 16 unaffected Dachshunds. Genotyping of three classical DLA class II genes (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was performed in 34 SARDS-affected and 66 unaffected Dachshunds to evaluate for an association in this region. Results: Although no single nucleotide polymorphisms (SNPs) were of genome-wide statistical significance (PBonferroni <0.05), 5 of the top 9 SNPs were in the major histocompatibility complex (MHC). Using DLA typing, the allele DLA-DRB1*09401 was identified as a risk factor for the development of SARDS (P = 0.0032, OR = 4.0). The alleles DLA-DQB1*00101 (P = 0.0050, OR = 0.31), DLA-DQA1*00901 (P = 0.0087, OR = 0.33), and a previously identified DLA-DRB1 allele described as “DRB1-T” (P = 0.0284, OR = 0.37) were identified as protective factors. Conclusions: Although far from definitive, association of SARDS with alleles of immunological importance further supports the hypothesis that autoimmunity may play a role in the pathogenesis of SARDS.

Canine sudden acquired retinal degeneration syndrome: Owner perceptions on the time to vision loss, treatment outcomes, and prognosis for life

“…One study did not find mixed breed dogs over‐represented compared with their hospital population, 6 and it is possible that this breed's overrepresentation reflects the high frequency of mixed breed dogs in the general population. In our study, the most common purebred dog breeds were the Dachshund, Miniature Schnauzer, and Pug, similar to other studies 6,8,15‐17 . We did not identify a seasonal incidence of SARDS in responses taken throughout the United States.…”

Presumed cancer‐associated retinopathy (CAR) mimicking Sudden Acquired Retinal Degeneration Syndrome (SARDS) in canines

“…Sudden acquired retinal degeneration syndrome was first reported almost four decades ago, and in recent years, there has been sufficient evidence characterizing it as an immune‐mediated type of retinopathy 5,6 . Blindness caused by SARDS is most frequently seen in middle‐aged/older females of small breeds, with mixed‐breed dogs, Dachshunds, Pugs, and Miniature Schnauzers being the most frequently affected 42 .…”

“…It is characterized by sudden‐onset blindness, completely extinguished retinal electrical responses, and the properties of abnormal chromatic pupil light reflex (cPLR) (no red PLR – good blue PLR) 1‐3 . It has been theorized that SARDs is an autoimmune disease similar to autoimmune retinopathies in humans (AIR), with a strong retinal autoantibody component 4‐8 …”

Le syndrome de la rétine silencieuse : revue bibliographique, actualités et perspectives

“…Une étude récente a permis d'identifier différents haplotypes du complexe majeur d'histocompatibilité de classe II conférant soit une protection vis-à-vis du SARDs soit une susceptibilité à l'égard de la maladie chez le Teckel. Ces résultats sont également en faveur d'une médiation immunitaire [19].…”