Multifocal retinopathy of Great Pyrenees dogs

Abstract

Forty‐four related Great Pyrenees dogs were examined ophthalmoscopically. Focal retinal elevations, multiple gray–tan–pink subretinal patches, and discrete areas of tapetal hyper‐reflectivity were seen in 19 dogs, ranging from 13 weeks to 10 years of age. These lesions varied in size from focal spots that were barely visible with the indirect ophthalmoscope to areas that were larger than the optic disc. Complete blood cell counts, serum biochemical profiles, urinalyses, and blood pressure measurements were completed on four affected dogs and all were within normal reference ranges. Photopic and scotopic electroretinography was completed and the a‐wave and b‐wave amplitudes and latencies were similar for affected and age‐matched nonaffected Great Pyrenees and other normal dogs. Electroretinograms that were examined twice during a 3‐year period on three affected adult dogs did not reveal significant progressive deterioration of the a or b‐wave parameters. Fluorescein angiography was completed on four affected dogs of ages 1 (n = 2), 5, and 6 years. These angiograms were repeated in three of these dogs 1 year later. The blood ocular barrier was intact in these dogs but there was blocked choroidal fluorescence. Postmortem examination, light microscopy, scanning and transmission electron microscopy were performed on three affected puppies and two affected adult dogs. These examinations revealed that the lesions in the puppies were limited to bilateral multiple areas of retinal pigment epithelial vacuolation, hypertrophy, and apparent separation from Bruch’s membrane, and multiple serous retinal detachments. The affected adult dogs had focal retinal degeneration and retinal pigment epithelial hypertrophy, hyperplasia and pigmentation. Pedigree analysis and test mating confirm that this condition is inherited, probably as an autosomal recessive trait. This condition develops at ≈ 13 weeks of age and the focal areas of retinal detachment and retinal pigment epithelial vacuolation progress to permanent and stable focal areas of retinal degeneration, and retinal pigment epithelial hypertrophy and pigmentation.

Multifocal retinopathy in Dachshunds with CLN2 neuronal ceroid lipofuscinosis

“…However, unlike in CMR, the retinal thinning in TPP1−/− dogs with extended survival times due to TPP1 administration to the CSF occurred across the entire retina and not just in the areas of the bullous detachments (unpublished). Fluorescein leakage from bullous lesions has not been observed in CMR (Grahn and Sandmeyer, 2006; Grahn et al, 2006) and was also not noted in the TPP1 −/− dogs affected with the retinopathy in this study.…”

“…Significant decreases in the thickness of the retina overlying these flattened bullous lesions were observed via sdOCT. The phenomenon of serous fluid loss from within the bullae and subsequent development of adjacent retinal thinning has also been noted in dogs with CMR (Grahn and Sandmeyer, 2006; Grahn et al, 2006). The resorptive/flattened lesions appeared in dogs with an average age of 12.3 months, which is a considerably advanced age for TPP1 −/− dogs.…”

“…Human disorders characterized by retinal lesions similar to those seen in the bestrophinopathies have also been associated with mutations in IMPG1 and PRPH2 (Manes et al, 2013; Meunier et al, 2011), but to date no mutations in these genes have been associated with CMR. CMR has been documented in many canine breeds including the Great Pyrenees (CMR1) (Grahn and Sandmeyer, 2006), Coton de Tulear (CMR2) (Grahn and Sandmeyer, 2006) and the Lapponian Herder (CMR3) (Zangerl et al, 2010). Most CMRs develop in the first year of life, and the retinopathy in this study appeared in TPP1 −/− dogs between the ages of 5 and 12 months and at an average age of 7.5 months.…”

AAV-Mediated Gene Therapy for Retinal Disorders in Large Animal Models

“…The condition develops at approximately 13 weeks of age and the focal areas of retinal detachment and RPE vacuolation progress to permanent and stable focal areas of retinal degeneration, RPE hypertrophy, and changes in RPE pigmentation. ERG measurements did not reveal signifi cant deterioration of the a-or b-wave parameters (Grahn and Cullen 2001;Grahn et al 1998).…”

Genetics of eye disorders in the dog.

“…Another inherited retinal disorder that is generally nonprogressive is canine multifocal retinopathy (CMR), a disease that has been recognized in several breeds, particularly Great Pyrenees, Coton de Tulear, English Mastiff and Bullmastiff [73,74]. Ophthalmoscopic changes are usually evident in affected dogs before the age of around 4 months and are characterized by multifocal areas of retinal elevation that contain subretinal accumulation of serous fluid.…”