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Objective: To describe ophthalmic, functional, structural, and genetical characteristics of progressive retinal atrophy (PRA) in the polski owczarek nizinny (PON) breed of dog., Animals Studied Clinically: Client-owned PON dogs (n = 82) from Sweden., Procedures: Routine examination for presumed inherited eye disease was performed in all dogs. Bilateral full-field electroretinography (ERG) was performed in 11 affected and 4 control dogs. Eyes from one affected dog were studied with light microscopy. DNA samples from 34 Swedish and 30 PON dogs collected by Michigan State University (MSU) were tested for the mutations causing the rcd4 and prcd forms of PRA., Results: Sixteen of the eighty-two Swedish dogs were diagnosed with PRA. Slight vascular attenuation, first seen at 4.5 years of age, preceded changes in tapetal reflectivity. The initial ERG changes in affected dogs showed markedly diminished rod responses, while cone responses were barely affected. Eventually, cone responses were also reduced. Retinal morphology showed approximately a 50% reduction of photoreceptor nuclei in the outer nuclear layer. Fourteen of fifteen PRA-affected Swedish dogs and eighteen of twenty of the MSU PRA-affected dogs tested genetically were positive for the rcd4 mutation. All tested dogs were negative for the mutation causing prcd-PRA., Conclusions: PRA of PON dogs is a late-onset degenerative disease with slow progression. There is early loss of rod function, while the cone system deteriorates later. The rcd4 mutation in the C2ORF71 gene was associated with the majority of the PRA cases tested. The possibility of additional forms of PRA in the breed cannot be excluded., (© 2015 American College of Veterinary Ophthalmologists.)

Purpose: Late infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder characterized by progressive vision loss. The disease results from mutations in the TPP1 (CLN2) gene. Studies were undertaken to characterize the effects of a TPP1 frameshift mutation on the retina in Dachshunds., Methods: A litter of four puppies consisting of one homozygous affected dog, two heterozygotes, and one homozygous normal dog were monitored for neurologic and retinal changes through 10 months of age. The affected and homozygous normal dogs, as well as one of the heterozygotes, were then euthanatized, and the retinas were examined morphologically., Results: The affected dog exhibited normal visual behavior and retinal function at 3 months of age, but vision was clearly impaired by 7 months, with markedly reduced ERG b-wave amplitudes. Beyond 7 months of age, the affected dog was functionally blind, and pupillary light reflexes and ERG response amplitudes continued to decline through 10 months of age. Both rod and cone system functions were severely impaired. The retina exhibited accumulation of autofluorescent storage bodies with distinctive curvilinear contents. Substantial cell loss occurred in the inner nuclear layer, with a smaller reduction in photoreceptor cell density., Conclusions: The canine TPP1 mutation results in progressive vision loss and retinal degeneration similar to that which occurs in human late infantile NCL. With the canine model, the natural history of disease progression in the retina provides a better understanding of the pathologic course of the disease and provides objective markers that can be used to assess the efficacy of therapeutic interventions.

Scanning-laser ophthalmoscopy is a technique for confocal imaging of the eye in vivo. The use of lasers of different wavelengths allows to obtain information about specific tissues and layers due to their reflection and transmission characteristics. In addition, fluorescent dyes excitable in the blue and infrared range offer a unique access to the vascular structures associated with each layer. In animal models, a further enhancement in specificity can be obtained by GFP expression under control of tissue-specific promotors. Important fields of application are studies in retinal degenerations and the follow-up of therapeutic intervention.

Aim: To assess retinal structure and function over a 3-year period in a group of five RPE65-/- dogs treated by unilateral rAAV- mediated subretinal gene transfer., Methods: Post-operative functional follow-ups were performed using simultaneous, bilateral, full-field ERGs. Structure was evaluated by SLO using FL and ICG angiography and by EM., Results: Significant improvement of retinal function was observed through ERGs approximately 4 weeks following surgery. Scotopic b-wave amplitudes peaked 3 months after surgery. Then there was a successive reduction, although greater amplitudes than base-line values were observed at all post-operative time points. A-wave amplitudes increased at a later time than b-wave amplitudes and were sustained throughout the follow-up period. The increased cone function was preserved longer than the rod function. Angiography showed structural changes at the site of injection, corroborated by photoreceptor destruction observed ultrastructurally. Immediately adjacent to the subretinal injection area photoreceptor outer segments appeared normal., Conclusion: Despite local structural alterations at the subretinal injection site, subretinal gene transfer in the RPE65 null mutation dog effectively increases retinal function for at least 3 years after surgery.

A 11‐year‐old neutered male Labrador retriever‐cross dog was presented to the University of Missouri‐Columbia Veterinary Ophthalmology Service for subtle visual deficits. Indirect ophthalmoscopy revealed a smooth, bullous elevation in the superior‐temporal retina OU. Optical coherence tomography (OCT) performed OU showed inner retinal separation consistent with retinoschisis. Electroretinography (ERG) revealed markedly reduced b‐wave amplitudes in the more severely affected eye (OD) compared with the less severely affected eye (OS). The most notable reductions were in the rod response and 30‐Hz flicker b‐waves OD which were approximately 50% of the corresponding amplitudes OS. Implicit times, particularly the a‐wave implicit times, were noticeably longer OD compared with OS. Lesions remained unchanged over 4 months at which time the dog was humanely euthanized for reasons unrelated to the ocular disease. Significant light microscopic ocular findings were bilateral superior temporal peripheral retinoschisis. The separation of the retinal tissue was similar between eyes and effectively divided the outer plexiform layer. In addition, thinning of the surrounding retinal layers was present. To the authors' knowledge, this is the first case of canine retinoschisis diagnosed with OCT, evaluated with electroretinography, and confirmed with light microscopic examination. History, clinical, and diagnostic findings, with the absence of disease progression over time, are analogous with cases of acquired senile retinoschisis in humans. [ABSTRACT FROM AUTHOR]

The article reports on an investigation of the clinical and electroretinographic (ERG) features of the retina in normal and progressive retinal atrophy (PRA) in canines. Topics discussed include the different classifications of PRA, the way animals in the authors' study were prepared for ERG, and the results of the ophthalmoscopic examination. Also mentioned is the methodology used by the authors in their study.

Objective To understand how progressive rod cone degeneration due to a mutation in CEP290 affects the pupillary light reflex (PLR) in domestic cats. Animals studied Domestic cats identified as either normal wildtype (WT; n = 6), or homozygous for the rdAc mutation in CEP290 and having early stage retinal degeneration (stage 2, S2; n = 4), or advanced retinal degeneration (S4; n = 6). Methods The effect of light on pupil size was measured over a series of 10-s pulses of white and chromatic light in cats lightly sedated with medetomidine. Results In WT cats, the PLR was characterized by a pronounced initial constriction that rapidly re-dilated during the stimulus (pupil escape), to a stable or sustained constriction. There was then a marked constriction at stimulus offset. Each component of the PLR was retained in affected cats, but with progressively reduced irradiance sensitivity from early to advanced retinal disease. Conclusions The PLR of cats had multiple phases, with a remarkably high-amplitude ‘paradoxical’ off-constriction even in the absence of retinal disease. In rdAc cats, reduced irradiance sensitivity was consistent with progressive loss of rod and cone function. Based on previously characterized retinal pathology, this suggests the visual streak of the retina has a proportionally large contribution to PLR input. These findings support the hypothesis that the efficacy of planned therapeutic trials can be determined by careful evaluation of the PLR in cats. [ABSTRACT FROM AUTHOR]

Objective To characterize hereditary retinal degeneration in the Abyssinian cat ( rdAc) in a recently established closed colony segregating for the rdAc mutation, and evaluate possible differences in the age of onset and progression of disease phenotype since the initial description of rdAc 25 years ago. The sample size of an earlier study was increased in order to determine the allele frequency in Abyssinian and Somali cats on a worldwide basis. Animals studied Twenty rdAc affected cats from the closed animal facility, 87 Abyssinian and Somali cats for study of genotype–phenotype concordance, and DNA from 131 Abyssinian and Somali cats from Scandinavia, the UK and Australia for evaluation of the rdAc allele frequency. Procedures DNA was extracted from blood and buccal swabs using commercially available kits, followed by genotyping. Ophthalmic examinations were performed in the USA and Sweden by two board-certified veterinary ophthalmologists. Results A greater variation in the age of onset and progression of the disease was observed compared to that previously described. An excellent correlation between genotype and phenotype was observed. A population genetic survey revealed that the rdAc allele is in moderate abundance in the Abyssinian breed in Europe and Australia. Surprisingly, homozygosity for the mutant allele was observed in a Siamese cat with ophthalmoscopic findings similar to those originally described for affected rdAc individuals. Conclusions Alertness to the potential of rdAc is needed on the part of the veterinary ophthalmology community, not only in Abyssinian and Somali cats but possibly also in other related cat breeds. [ABSTRACT FROM AUTHOR]

Abstract: Blood flow in the choroid of eyes with retinal degeneration is normally reduced. In the Abyssinian cat, where no changes in choroidal blood flow were observed recently, a closer morphological analysis revealed that two factors might have lead to this finding. (a) The cat''s eye consists of a tapetum lucidum where 15.5μm microspheres cannot reach the precapillary branching in contrast to the non-tapetal areas, where microspheres were located right next to the choriocapillaris. This fact has not yet been described and might be important for further physiological measurements in eyes of species with a tapetum lucidum. (b) The tapetal cells themselves might have a protective role for the choriocapillaris and RPE during retinal degeneration in this specific animal model. Even in late stages of retinal degeneration the RPE and choriocapillaris in areas covered by the tapetum lucidum were not affected whereas non-tapetal areas showed loss of RPE and capillaries. [Copyright &y& Elsevier]

Purpose : The purpose of this study was to investigate morphological changes of the anterior segment of the eye in Abyssinian cats with progressive rod-cone degeneration and to correlate them with blood flow data obtained in the same animals. Methods : Sections of the left eyes of six normal cats and of eight cats with different stages of hereditary retinal degeneration were prepared for transmission and scanning electron microscopy. Tangential and sagittal sections were also stained with antibodies against substance P, tyrosine hydroxylase, panneuronal marker PGP9.5, nitric oxide synthase, synaptophysin, and smooth muscle α -actin. Results : In Abyssinian cats with hereditary rod-cone degeneration, significant changes were observed in the iris consisting of irregularities in the vascular wall of smaller arteries without changes in their innervation pattern. The ciliary processes were shorter than in normal cats, and their structure appeared more compact and retracted. Slight changes were also observed in the anterior part of the ciliary epithelium. The anterior chamber angle region did not appear to be affected. Conclusions : Clear morphological correlations to the physiological blood flow data were observed in the anterior eye segment, pointing not only to functional but also morphological vascular abnormalities in this animal model for retinitis pigmentosa. [ABSTRACT FROM AUTHOR]

Aim: To determine the diagnostic efficiency of scores in a long protocol electroretinogram (ERG) for Abyssinian cat slow recessive rod/cone dystrophy. Methods: Kittens (n = 22) were bred from homozygous, affected and heterozygous normals. Ophthalmoscopy was regularly performed and disease signs noted. Cats (age ≥ 8 months, 40 sessions, 1-3 repeats) were dark-adapted overnight, anaesthetized and simultaneous binocular ERG recorded using a long protocol. Conventional a- and b-amplitudes and peak implicit times were measured and b/a ratios calculated, initially only for ERG to the maximum photopic and scotopic stimulus Principal components factor analysis was applied to various subsets of these scores plus age attesting. Results: Six cats with ophthalmoscopic change were classed as affected. Three cats, one tested three times, were suspect. The rest were considered normal. The first analysis, of 80 eyes and 37 parameters, showed that the first factor was the only effective one. Using it, the groups overlapped 5%, scotopic amplitudes and b/a ratios loaded higher than peak times, the eyes were very similar, and age and photopic b/a ratios loaded poorly. The groups were discriminable with all the data. A second analysis, with eyes averaged and the 20 measures loading over 0.5 on the first factor, showed better group separation on factor I alone. An iterative search with varying data sets found that factor I was optimal, with eight ERG measures to the three brightest scotopic and one brightest photopic response. It produced a large absolute separation and classified the suspects consistently. With b/a ratios on these four ERG also included, 12 parameters gave better separation. Conclusion: Twelve scores on four ERG separate affected from normal cats with a wide gap and consistently classify suspects. It may work for earlier ages. Additional data probably adds noise. This combination of optimal scores needs confirmation in new data [ABSTRACT FROM AUTHOR]

To study retinal function in cats homozygous and heterozygous for a recessively inherited rod-cone degeneration. Dark-adapted electroretinograms (ERGs) were performed on early affected, heterozygous (ophthalmoscopically normal), and clinically normal, nonrelated cats. Responses to blue stimuli over a 3.9-log unit range were recorded. Lower b-wave amplitudes than normal were observed in heterozygotes and early affected cats. The amplitudes of the heterozygotes took an intermediate position between normal and early affected cats. Normalized amplitude/intensity data suggest a normal dynamic range in carriers. B-wave implicit times in carriers were comparable to those of normal cats. These results show that heterozygotes have an altered retinal function, although they are ophthalmoscopically normal. It is difficult to electrophysiologically differentiate heterozygotes from affected cats with the very early stage of retinal degeneration. [ABSTRACT FROM AUTHOR]

Abstract Neuroretinal transplantation techniques have been evolving during recent years. Experiments in rodent models with degenerative retinal disease have been encouraging. This paper describes a surgical technique developed for use in the Abyssinian cat mutant. After two-port pars plana vitrectomy, retinotomy and bleb formation, whole sheets of neonatal neuroretinal allografts were placed into the subretinal space. The surgery was difficult but feasible, and the main complication was intraoperative hemorrhage. [ABSTRACT FROM AUTHOR]