Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic expression

Dostal, Jesse; Hrdlicova, A.; Horák, Pavel

doi:10.17221/1564-vetmed

Cited by 13 publications

(17 citation statements)

References 7 publications

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“…photoreceptor | PRCD | retinal degeneration | microglia P rogressive rod-cone degeneration (PRCD) is a canine retinal disease and the most common known cause of blindness in dogs, affecting over 35 breeds with allelic frequency as high as 45% (1)(2)(3)(4)(5). The disease is caused by a single C2Y mutation in the Prcd gene, which is expressed specifically in the retina (6,7).…”

mentioning

confidence: 99%

PRCD is essential for high-fidelity photoreceptor disc formation

Spencer

Ding

Lewis

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Progressive rod-cone degeneration (PRCD) is a small protein residing in the light-sensitive disc membranes of the photoreceptor outer segment. Until now, the function of PRCD has remained enigmatic despite multiple demonstrations that its mutations cause blindness in humans and dogs. Here, we generated a PRCD knockout mouse and observed a striking defect in disc morphogenesis, whereby newly forming discs do not properly flatten. This leads to the budding of disc-derived vesicles, specifically at the site of disc morphogenesis, which accumulate in the interphotoreceptor matrix. The defect in nascent disc flattening only minimally alters the photoreceptor outer segment architecture beyond the site of new disc formation and does not affect the abundance of outer segment proteins and the photoreceptor’s ability to generate responses to light. Interestingly, the retinal pigment epithelium, responsible for normal phagocytosis of shed outer segment material, lacks the capacity to clear the disc-derived vesicles. This deficiency is partially compensated by a unique pattern of microglial migration to the site of disc formation where they actively phagocytize vesicles. However, the microglial response is insufficient to prevent vesicular accumulation and photoreceptors of PRCD knockout mice undergo slow, progressive degeneration. Taken together, these data show that the function of PRCD is to keep evaginating membranes of new discs tightly apposed to each other, which is essential for the high fidelity of photoreceptor disc morphogenesis and photoreceptor survival.

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mentioning

confidence: 99%

PRCD is essential for high-fidelity photoreceptor disc formation

Spencer

Ding

Lewis

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been reported that ECS are affected by a relatively late onset and slowly progressive form of PRA, as demonstrated by late changes on funduscopy, areas of delayed retinal degeneration on histology and delayed loss of the b‐wave function on ERG in comparison to other breeds . There is a relatively high prevalence of prcd mutations in this breed, which is a late‐onset form of PRA . In the present study, all of the dogs included were ECS which is a very popular breed in the United Kingdom and one of the most common dog breeds presented to the RVC during the period of the study.…”

Section: Discussionmentioning

confidence: 80%

“…17,19 There is a relatively high prevalence of prcd mutations in this breed, which is a late-onset form of PRA. 16,21 In the present study, all of the dogs included were ECS which is a very popular breed in the United Kingdom and one of the most common dog breeds presented to the RVC during the period of the study. When counseling the owners, it was discussed that the visual outcome and how long the dog could remain visual post-surgery were unknown at the time.…”

Section: Discussionmentioning

confidence: 99%

Visual outcome following phacoemulsification in English Cocker Spaniels with suspected progressive retinal atrophy: A retrospective multicenter study of 54 cases (2002‐2017)

Koll-Hampp

Enache

Fenollosa-Romero³

et al. 2019

Veterinary Ophthalmology

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Objective To describe the visual outcome following phacoemulsification in English Cocker Spaniels (ECS) affected by cataracts and suspected progressive retinal atrophy (PRA). Animals studied Fifty‐four client‐owned dogs. Procedures A multicenter, retrospective study was performed including ECS with suspected PRA which underwent phacoemulsification. PRA was suspected on ophthalmic examination before and after surgery, and/or after electroretinography (ERG) was performed. Visual outcome was assessed by menace response per eye at seven time periods post‐surgery (P1= 25‐90 days, P2 = 91‐180 days, P3 = 181‐364 days, P4 = 365‐549 days, P5 = 550‐729 days, P6 = 730‐1094 days, and P7 ≥ 1095 days). Descriptive statistics were performed. Generalized estimating equations were used to identify predictors associated with vision after surgery. Odds ratio and confidence intervals were reported. Significance was set at P < 0.05. Owners were invited to participate in a questionnaire. Results Phacoemulsification was performed in 85 eyes. Median age at surgery was 9.09 years (min. 2.17 years, max. 13.49 years). At all re‐examinations, up to and including P5, significantly more eyes were visual than before surgery (P ≤ 0.003). Odds for vision were significantly increased for eyes that underwent surgery. Electroretinograms were performed in 75/85 eyes that underwent surgery, demonstrating low b‐wave amplitudes. There was no significant effect of the age, gender, vision before surgery, presence of dazzle reflex, cataract stage or abnormality on gonioscopy on visual outcome. The questionnaire response rate was 48.2%. Most participants (92.5%) felt that cataract surgery led to improvement of the dog's quality of life. Conclusions English Cocker Spaniels with suspected PRA may benefit from phacoemulsification with vision up to 2 years following surgery.

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“…They are one of the >60 breeds of dogs that carry the mutation in PRCD resulting in a late-onset PRA within the breed. 4,11,12 The genetic test for PRCD has been available to the SWD breeders for over 10 years, and it has been utilized to aid in breeding programs to remove the mutation from the SWD population (swdclub.org).…”

Section: Discussionmentioning

confidence: 99%

A novel mutation in PDE6B in Spanish Water Dogs with early‐onset progressive retinal atrophy

Winkler

Ramsey

Petersen‐Jones

2020

Veterinary Ophthalmology

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Objective To identify the underlying mutation in a recently identified early‐onset progressive retinal atrophy (PRA) in the Spanish Water Dog (SWD) breed. Animal Studied Eighteen SWDs were used in this study. Six SWDs diagnosed with PRA and 12 phenotypically normal SWDs. Procedures An exclusion analysis using an established microsatellite panel to screen PRA candidate genes was combined with whole genome sequencing of two affected SWD siblings and two phenotypically normal SWDs (a sibling and the dam). Results A 6‐bp deletion was identified in exon 19 of PDE6B removing two highly conserved amino acids from the enzymatic domain of the PDE6B protein (c.2218‐2223del; p.Phe740_Phe741del). This segregated with the disease status in the small study pedigree. Conclusions Identification of this novel PDE6B mutation adds to the already described PDE6B mutations responsible for PRA in the Irish Setter, Sloughi, and American Staffordshire Terrier dog breeds. A DNA‐based test was designed to allow breeders to genotype their animals and make informed breeding decisions in the effort to eradicate PRA from the SWD breed.

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Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic expression

Cited by 13 publications

References 7 publications

PRCD is essential for high-fidelity photoreceptor disc formation

PRCD is essential for high-fidelity photoreceptor disc formation

Visual outcome following phacoemulsification in English Cocker Spaniels with suspected progressive retinal atrophy: A retrospective multicenter study of 54 cases (2002‐2017)

A novel mutation in PDE6B in Spanish Water Dogs with early‐onset progressive retinal atrophy

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