The electroretinographic phenotype of dogs with Golden Retriever muscular dystrophy

Objective To characterize the flash electroretinogram (ERG) in the Golden Retriever muscular dystrophy (GRMD) dog and to compare the results with those from a control group of Golden Retrievers. To investigate whether similar abnormalities of the ERG as those found in a majority of human patients with Duchenne muscular dystrophy (DMD) are also observed in the GRMD dog, the canine model for DMD. Animals Five GRMD dogs and five age‐matched clinically normal Golden Retrievers. Procedure An ophthalmic examination was carried out prior to performing electroretinography under general anesthesia. Rod, combined rod–cone and oscillatory potentials responses were recorded after dark adaptation. Responses to 30‐Hz‐flicker were recorded after light adaptation. The ERG responses of the GRMD dogs were compared with those of the control dogs by use of a Wilcoxon signed rank test. Results GRMD dogs had significantly reduced a and b‐wave amplitudes after dim white flash stimuli (rod response) and reduced a‐wave amplitude after bright white flash stimuli (rod–cone response). Conclusion and clinical relevance The ERG abnormalities observed in the GRMD dog suggest a dysfunction in the rod signaling pathway. These ERG alterations are different from those observed in human patients with DMD.     

Retinal degeneration in nine Swedish Jämthund dogs

The Jämthund is the fourth most common breed in Sweden with approximately 1600 pups registered each year. Although it has been known that some adult dogs go blind, so they cannot hunt, the Jämthund dog has historically not been screened for hereditary eye diseases. This report describes nine Swedish Jämthund dogs with retinal degeneration. These dogs represent all Jämthund dogs diagnosed with progressive retinal atrophy (PRA) by the Swedish Eye Panel and registered with the Swedish Kennel Club from January 1998 to September 2008. The dogs were examined with indirect opthalmoscopy and slitlamp biomicroscopy. Additionally, electroretinograms (ERGs) following ECVO guidelines were performed in two dogs (one affected and one normal) and the eyes from three affected dogs were examined by light‐microscopy postmortem. Typical findings were bilateral symmetric generalized retinal degeneration with tapetal hyper‐reflectivity, attenuation of blood vessels and pigment clumping in the nontapetal fundus. These retinal findings progressed with time in two dogs after re‐examination. Visual impairment, especially under dim light conditions, was observed in the affected dogs. ERG from one affected dog showed profoundly reduced rod responses, whereas cone responses were better preserved. Microscopic changes in the eyes from three dogs were characterized by a severe diffuse predominantly outer retinal degeneration and atrophy. Re‐sequencing of the prcd‐gene for eight of the nine investigated dogs revealed that none of the individuals carried disease allele that has been associated with prcd‐PRA in other breeds. In conclusion, ophthalmoscopic, electroretinographic, and light‐microscopic alterations observed in nine Jämthund dogs were compatible with PRA. The prcd mutation was excluded as a cause of this retinopathy.     

A truncated retrotransposon disrupts the GRM1 coding sequence in Coton de Tulear dogs with Bandera's neonatal ataxia

Background: Bandera's neonatal ataxia (BNAt) is an autosomal recessive cerebellar ataxia that affects members of the Coton de Tulear dog breed. Objective: To identify the mutation that causes BNAt. Animals: The study involved DNA from 112 Cotons de Tulear (including 15 puppies with signs of BNAt) and 87 DNA samples from dogs of 12 other breeds. Methods: The BNAt locus was mapped with a genome‐wide association study (GWAS). The coding exons of positional candidate gene GRM1, which encodes metabotropic glutamate receptor 1, were polymerase chain reaction (PCR)‐amplified and resequenced. A 3‐primer PCR assay was used to genotype individual dogs for a truncated retrotransposon inserted into exon 8 of GRM1. Results: The GWAS indicated that the BNAt locus was in a canine chromosome 1 region that contained candidate gene GRM1. Resequencing this gene from BNAt‐affected puppies indicated that exon 8 was interrupted by the insertion of a 5′‐truncated retrotransposon. All 15 BNAt‐affected puppies were homozygous for the insert, whereas all other Cotons de Tulear were heterozygotes (n = 43) or homozygous (n = 54) for the ancestral allele. None of the 87 dogs from 12 other breeds had the insertion allele. Conclusions and Clinical Importance: BNAt is caused by a retrotransposon inserted into exon 8 of GRM1. A DNA test for the GRM1 retrotransposon insert can be used for genetic counseling and to confirm the diagnosis of BNAt.     

A slowly progressive retinopathy in the Shetland Sheepdog

Objective To describe a slowly progressive retinopathy (SPR) in Shetland Sheepdogs. Animals Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of SPR and six normal Shetland Sheepdogs were included in the study. Procedure Ophthalmic examination including slit‐lamp biomicroscopy and ophthalmoscopy was performed in all dogs. Electroretinograms and obstacle course‐test were performed in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups according to their dark‐adapted b‐wave amplitudes. SPR1‐dogs had ophthalmoscopic signs of SPR, but normal dark‐adapted b‐wave amplitudes. Dogs with both ophthalmoscopic signs and subnormal, dark‐adapted b‐wave amplitudes were assigned to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination. Results The ophthalmoscopic changes included bilateral, symmetrical, greyish discoloration in the peripheral tapetal fundus with normal or marginally attenuated vessels. Repeated examination showed that the ophthalmoscopic changes slowly spread across the central parts of the tapetal fundus, but did not progress to obvious neuroretinal thinning presenting as tapetal hyper‐reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed significantly reduced b‐wave amplitudes throughout dark‐adaptation. Microscopy showed thinning of the outer nuclear layer and abnormal appearance of rod and cone outer segments. Testing for the progressive rod–cone degeneration ( prcd )‐mutation in three dogs with SPR was negative. Conclusion Slowly progressive retinopathy is a generalized rod–cone degeneration that on ophthalmoscopy looks similar to early stages of progressive retinal atrophy. The ophthalmoscopic findings are slowly progressive without tapetal hyper‐reflectivity. Visual impairment is not obvious and the electroretinogram is more subtly altered than in progressive retinal atrophy. The etiology remains unclear. SPR is not caused by the prcd‐mutation.     

Effects of hereditary retinal degeneration due to a CEP290 mutation on the feline pupillary light reflex

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.     

Furosemide loading test in a case of homozygous solute carrier family 12, member 1 (SLC12A1) mutation (g.62382825G>A,p.Pro372Leu) in Japanese Black cattle

Hydrallantois is the excessive accumulation of fluid in the allantoic cavity in a pregnant animal and is associated with fetal death. We recently identified a recessive missense mutation in the solute carrier family 12, member 1 (SLC 12A1 ) gene (g.62382825G>A, p.Pro372Leu) that is associated with hydrallantois in Japanese Black cattle. Unexpectedly, we found a case of the homozygous risk‐allele for SLC 12A1 in a calf, using a PCR ‐based direct DNA sequencing test. The homozygote was outwardly healthy up to 3 months of age and the mother did not exhibit any clinical symptoms of hydrallantois. In order to validate these observations, we performed confirmation tests for the genotype and a diuretic loading test using furosemide, which inhibits the transporter activity of the SLC 12A1 protein. The results showed that the calf was really homozygous for the risk‐allele. In the homozygous calf, administration of furosemide did not alter urinary Na⁺ or Cl^? levels, in contrast to the heterozygote and wild‐type calves in which these were significantly increased. These results demonstrate that the SLC 12A1 (g.62382825G>A, p.Pro372Leu) is a hypomorphic or loss‐of‐function mutation and the hydrallantois with this mutation shows incomplete penetrance in Japanese Black cattle.     

Clinical findings in early onset cone-rod dystrophy in the Standard Wire-haired Dachshund

OBJECTIVE: To describe the clinical findings and the age of onset of cone-rod dystrophy (crd) in the Standard Wire-haired Dachshund (SWHD) and to evaluate which clinical tests could be used to obtain a reliable diagnosis. ANIMALS: Sixty-eight SWHD and SWHD-derived dogs were used, including 23 affected with crd and 45 controls, respectively. PROCEDURES: The dogs were subjected to behavioral testing, examination of pupillary light reflexes (PLRs), indirect ophthalmoscopy and bilateral full field electroretinography (ERG). RESULTS: The majority of affected puppies (5-10 weeks) displayed pin-point sized pupils upon examination with focal light. All dogs in the control group, except one, displayed normal PLRs upon examination. In all crd-affected dogs there was a great variation both in age of onset and in clinical appearance of retinal changes upon fundoscopy. Two siblings displayed panretinal degeneration at the age of 10 months while other affected dogs showed early changes at the age of 3 years. Generalized bilateral retinal atrophy was the end stage of the disease. The maze test revealed no obvious differences among affected and unaffected groups. ERG recordings showed only slightly reduced rod, and mixed rod-cone responses, but severely reduced cone single flash a- and b-wave amplitudes, and cone flicker amplitudes were observed in all affected dogs. CONCLUSION: Presence of pin-point sized pupils in young SWHDs was found to be an important indicator of early onset crd. Fundoscopic changes and progression of disease at later stages resembled those previously described in the majority of progressive retinal atrophies in dog. ERG was found to be the most reliable diagnostic procedure to clinically diagnose crd in the SWHD.     

Electroretinography recordings using a light emitting diode active corneal electrode in healthy beagle dogs

Electroretinography (ERG) is a well-established diagnostic procedure for objectively evaluating retinal function. In this study, ERG in beagle dogs, which are a popular experimental animal, was performed to determine the normal range of ERG variables and assess differences between the left and right eyes. ERG findings including rod, combined rod-cone, single-flash cone, and 30-Hz flicker responses were recorded with an LED-electrode in 43 sedated beagle dogs. The subjects were divided into young (< 1 year old), adult (1~5 years old), and senile animals (≥ 6 years old). Normal ERG ranges were obtained. Significant differences in b-wave amplitude along with b/a ratio of the combined rod-cone response were found between the young and adult animals as well as young and senile dogs. No significant differences were observed between the left and right eyes. ERG variables in beagle dogs differed by age due to age-related retinal changes. Thus, we propose that normal ERG ranges should be determined according to age in each clinic and laboratory using its own equipment because each institution usually has different systems or protocols for ERG testing.     

Electroretinographic changes after intravenous lipid emulsion therapy in a dog and a foal with ivermectin toxicosis

This case report describes ivermectin‐induced blindness in a dog and a foal with normal ophthalmic fundic examinations and attenuated electroretinography (ERG). Subsequent recovery in ERG was noted following intravenous lipid emulsion (ILE) therapy. A dog and a foal were evaluated for ivermectin‐induced blindness. Clinical signs included dull mentation, absent pupillary light reflexes (PLRs), and absent menace on presentation. The animals had normal fundoscopic examinations; however, in both cases ERG was consistent with neurosensory retinal dysfunction. Following ILE therapy for ivermectin toxicosis, return of menace, PLRs, and normal mentation were noted, as was improvement in ERG and serum ivermectin levels. These are the first documented cases of ivermectin‐induced blindness in a dog and a foal with normal fundic examinations and attenuated ERG. ERG improved in both animals after ILE therapy. ERG may assist in the diagnosis of ivermectin toxicosis in dogs and horses. ILE therapy may hasten recovery in treatment of ivermectin‐induced blindness.     

Electroretinography using contact lens electrode with built-in light source in dogs

Electroretinography (ERG) is an effective method for the diagnosis of retinal disease. In the dog, dependable ERG recording is difficult without the use of an expensive device like a Ganzfeld full-field stimulator. The International Society for Clinical Electrophysiology of Vision has defined the standard flash stimulus condition (SF) and evaluation of the retina using the b/a ratio in humans. In dogs, evaluation using the b/a ratio has not been reported, whereas the intensity of SF has been defined. In this study, we performed a convenient ERG recording method using a contact lens electrode with a built-in light source (LED-electrode), and confirmed SF as reported previously. ERG recordings were performed on 15 healthy beagle dogs under sedation. We performed bilateral ERG at 12 different intensities after 30 min dark adaptation. After 10 min light adaptation, we recorded single flash cone and flicker cone response using the SF determined in this study. In this study, SF of 3.0 cd/m(2)/sec (6,000 cd/m(2), 0.5 msec) resulted in b/a=2. The intensity for rod response that recorded only the b-wave was 0.0096 cd/m(2)/sec (80 cd/m(2), 0.12 msec). We could achieve ERG for each response easily and smoothly under sedation, and without general anesthesia. Using an LED-electrode, we could perform more quantitative and reproducible ERG examinations than with traditional methods. We propose that the b/a ratio is the most useful parameter in ERG reporting for evaluating retinal function.     

Canine multifocal retinopathy caused by a BEST1 mutation in a Boerboel

A 7‐month‐old male intact Boerboel presented to the Cummings School of Veterinary Medicine at Tufts University for the evaluation of ocular discharge. Bilateral multifocal serous retinal detachments were noted on fundus examination as an incidental finding. Genetic testing confirmed the dog to be homozygous for a mutation in the BEST1 gene, where a C₇₃T/R₂₅X change results in premature termination codon. Further testing, including electroretinography and optical coherence tomography (OCT), demonstrated that there was no evidence of retinal photoreceptor dysfunction and confirmed that observed lesions were characteristic of canine multifocal retinopathy. No progression of the lesions was noted 3 months after the initial examination. To the authors’ knowledge, this is the first report of canine multifocal retinopathy in the Boerboel breed.     

Detection of cone dysfunction induced by digoxin in dogs by multicolor electroretinography

It is difficult to detect discrete cone function with the present conventional electroretinography (ERG) examination. In this study, we developed contact electrodes with a built-in color (red (644 nm), green (525 nm), or blue (470 nm)) light source (color LED-electrode), and evaluated an experimental model of digoxin in the dog. First, 17 normal Beagle dogs were used to determine which electrode works well for color ERG measurement on dogs. Then, color ERG was performed on seven normal Beagle dogs at various points during a 14-day period of digoxin administration. A single daily dose of 0.0125 mg/kg/day, which is within the recommended oral maintenance dosage range for dogs, was administered orally for 2 weeks. Ophthalmic examination, measurement of plasma concentration of digoxin, and color ERG examination were performed. On first examination, amplitudes of all responses were significantly (P < 0.01) lower with the red, than with the blue and green electrodes during ERG recording. In ERG using the red electrode, the standard deviation was large. According to these preliminary results, the red electrode was not used in the experimental dog model with digoxin. In the digoxin administrated animals, no significant change was observed in the ophthalmic examination findings. The digoxin level increased steadily throughout the dosing period but was always within the therapeutic range for dogs. In rod ERG, no abnormalities were detected with any electrode. In standard combined ERG, decreased amplitude of the a-wave was detected with every electrode. In single flash cone ERG, prolongation of implicit time was detected by color ERG with the blue and green electrodes. In 30-Hz flicker ERG, decreased amplitude was detected only by color ERG with the blue electrode. The decreased amplitude and prolonged implicit time recovered after termination of digoxin administration. Cone dysfunction induced by digoxin in the dog was revealed by multicolor ERG using blue and green LED-electrodes. Multi-color ERG was useful for detecting cone type-specific dysfunction in the dog.     

Immunological and angiogenic markers during metronomic temozolomide and cyclophosphamide in canine cancer patients

Metronomic chemotherapy stimulates the immune response via depletion of regulatory T cells (Tregs) and suppresses angiogenesis by modulating the secretion of thrombospondin‐1 (TSP‐1) and vascular endothelial growth factor (VEGF). In this study, blood was collected from 10 healthy dogs and from 30 canine cancer patients before and 2 and 4 weeks after treatment with metronomic temozolomide (6.6 mg m^?2), cyclophosphamide (12.5 mg m^?2) or cyclophosphamide and temozolomide. The percentage of circulating CD25⁺Foxp3⁺CD4⁺ Tregs and the plasma levels of TSP‐1 and VEGF were measured. There was a significant difference in the percentage of Tregs between cancer patients and healthy dogs. A significant decrease in Tregs was noted in patients treated with metronomic cyclophosphamide and the combination. Treatment with temozolomide had no effect on the percentage of Tregs. TSP‐1 and VEGF levels were, respectively, significantly lower and higher in cancer patients than in healthy dogs, but they were not influenced by any of the studied metronomic treatment regimens.     

Gain‐of‐function mutation in PTPN11 in histiocytic sarcomas of Bernese Mountain Dogs

Histiocytic sarcoma (HS) is an aggressive malignant neoplasm of dendritic cell origin that is common in certain breeds of dogs. High prevalence of fatal, disseminated HS has been described in Bernese Mountain Dogs (BMDs). Support for genetic predisposition to develop HS has been presented in several studies, but to date, causative genetic events have not been reported. In addition, no driver mutations have been identified in tumours. Recently, E76K gain‐of‐function mutation in SHP2 encoded by the PTPN11 gene has been described in human histiocytic malignancies. In our study, we identified the PTPN11^E76K in HS of BMDs. Amplification of exon 3 of the PTPN11 gene followed by Sanger sequencing was used to detect the mutation and estimate the prevalence in HS from 30 BMDs, 13 Golden Retrievers and 10 other dog breeds. The overall prevalence of PTPN11^E76K in HS of BMDs was 36.67% compared with 8.69% in other breeds. No mutation was identified in normal tissues from 10 BMDs with HS that carried the mutation and 12 control dogs with no neoplastic disease, including 6 BMDs. Increased immunoreactivity for AKT, phosphorylated ERK1/2 and phosphorylated AKT in a small subset of BMDs with PTPN11^E76K suggests that a gain‐of‐function might be mediated by the ERK and AKT pathways. These data suggest PTPN11^E76K as an important driver mutation of HS in BMDs. This information may not only aid in unravelling the tumourigenic events associated with HS in BMDs, but also help in identifying more promising therapeutic strategies.     

ERG findings in three hypothyroid adult dogs with and without levothyroxine treatment

Purpose To evaluate the effects of levothyroxine (LTh) on the electroretinogram (ERG) of adult dogs. Material and methods Binocular, full field photopic and scotopic ERGs were recorded from an anesthetized Maltese Bichon cross (MB), a Yorkshire Terrier (YT) and a Shetland Sheepdog (SS) affected with hypothyroidism and treated with a daily dose of LTh at 20 µg/kg. The photopic ERGs were evoked to 12 different intensities ranging from 0.81 to –2.19 log cd.s/m² and presented under photopic conditions in order to assess (from the derived luminance-response curves) Vmax and b : a amplitude ratio parameters. Photopic flicker ERGs were obtained at 30 Hz. The scotopic ERGs (intensity: –3.09 log cd.s/m²) were recorded while the retina was dark-adapting and after 32 min of dark adaptation. This procedure was performed on two separate sessions: following a 3-day interruption of LTh treatment (S1) and following 30 days without interruption of LTh treatment (S2). Results The mean photopic a-wave peak times were 9.8 ms at S1 and 5.0 ms at S2, respectively. The mean photopic b-wave peak times were 23.3 ms at S1 and 11.5 ms at S2, respectively, and the mean scotopic b-wave peak times (after 32 min of dark adaptation) were 45.2 ms at S1 and 26.0 ms at S2, respectively. No other significant ERG changes were observed. Conclusion Our results indicate that a dose of 20 µg/kg of LTh given to adult dogs was accompanied by a marked peak time shortening of both photopic and scotopic ERGs, without affecting other ERG parameters.     

Acute blindness in dogs: Sudden acquired retinal degeneration syndrome versus neurological disease (140 cases, 2000–2006)

Objective  To evaluate dogs with amaurosis and compare signalment, history, ophthalmic examination and neurologic abnormalities between dogs diagnosed with sudden acquired retinal degeneration syndrome (SARDS) versus neurological disease (ND). Animals Studied-140 dogs with acute vision loss and ocular abnormalities insufficient to account for visual deficits. An electroretinogram (ERG) was performed on each dog.
Procedures  Medical records were reviewed and information was collected for all dogs meeting the inclusion criteria. Dogs diagnosed with SARDS were compared to those with ND based on signalment, duration of clinical signs, past medical problems, clinicopathologic findings, and ophthalmic and physical examination abnormalities.
Results  120 dogs were diagnosed with SARDS and 20 dogs with ND based on ERG results. Mixed-breed dogs were most commonly diagnosed with SARDS as well as ND. Pure breed dogs frequently diagnosed with SARDS included the Miniature Schnauzer and Dachshund. Dogs with SARDS did not differ significantly from those with ND based on age or sex distribution. Cushing's-like symptoms were reported more frequently in SARDS dogs as well as conjunctival hyperemia and retinal vascular attenuation. Papilledema and asymmetric visual deficits were observed more frequently in dogs with ND. Dogs with ND were no more likely than SARDS dogs to have additional neurological deficits.
Conclusions  Appreciable overlap of clinical signs exists between dogs with SARDS and dogs with ND resulting in acute vision loss. As a significant portion of dogs (14%) in the present study were diagnosed with ND, an ERG to rule out ND is indicated in dogs with amaurosis.     

Comparing the photopic ERG i-wave in different species

The i‐wave, a post b‐wave component of the human photopic electroretinogram (ERG), is claimed to originate at the level of the retinal ganglion cells (RGC) or more distally. We investigated whether this wave is a feature common to all species. Photopic ERGs were obtained from the following species: Beagle dog, European cat, New Zealand white rabbit, Göttingen minipig, Cynomolgus monkey, Sprague–Dawley and brown Norway rats, Hartley guinea pig, and CD1 and C57BL6 mice. Results were compared with those obtained from normal human subjects. Except for rats and mice, all species yielded a well‐demarcated i‐wave, easily identifiable and separated from the a–b‐wave complex by ≈ 20 ms. Our sample suggests that the i‐wave is a feature common to the photopic ERG of most species including humans. In view of its suggested origin, the i‐wave would offer a unique opportunity to test, with the flash ERG, the functional integrity of the retinal ganglion cells in animals where use of a pattern stimulus is not always easily obtained.     

Characterization of the normal dark adaptation curve of the horse

Objective The goal of this work is to study the dark adaptation curve of the normal horse electroretinogram (ERG). Procedures The electroretinographic responses were recorded from six healthy female ponies using a contact lens electrode and a mini‐Ganzfeld electroretinographic unit. The horses were sedated intravenously with detomidine, an auriculopalpebral nerve block was then performed, and the pupil was fully dilated. The ERG was recorded in response to a low intensity light stimulus (30 mcd.s/m²) that was given at times (T) T = 5, 10, 15, 20, 25, 30, 40, 50, and 60 min of dark adaptation. Off‐line analysis of the ERG was then performed. Results Mean b‐wave amplitude of the full‐field ERG increased continuously from 5 to 25 min of dark adaptation. The b‐wave amplitude peaked at T = 25, however, there was no statistical significance between T = 20 and T = 25. The b‐wave amplitude then remained elevated with no significant changes until the end of the study at T = 60 (P > 0.49). The b‐wave implicit time increased continuously between T = 5 and T = 20, then gradually decreased until T = 60. No distinct a‐wave was observed during the testing time. Conclusions Evaluation of horse rod function or combined rod/cone function by means of full‐field ERG should be performed after a minimum 20 min of dark adaptation.     

Identification of a nonsense mutation in feline ABCB1

The aim of this study was to sequence all exons of the ABCB1 (MDR1) gene in cats that had experienced adverse reactions to P‐glycoprotein substrate drugs (phenotyped cats). Eight phenotyped cats were included in the study consisting of eight cats that experienced central nervous system toxicosis after receiving ivermectin (n = 2), a combination product containing moxidectin and imidacloprid (n = 3), a combination product containing praziquantel and emodepside (n = 1) or selamectin (n = 2), and 1 cat that received the product containing praziquantel and emodepside but did not experience toxicity (n = 1). Fifteen exons contained polymorphisms and twelve exons showed no variation from the reference sequence. The most significant finding was a nonsense mutation (ABCB11930_1931del TC) in one of the ivermectin‐treated cats. This cat was homozygous for the deletion mutation. All of the other phenotyped cats were homozygous for the wild‐type allele. However, 14 missense mutations were identified in one or more phenotyped cats. ABCB11930_1931del TC was also identified in four nonphenotyped cats (one homozygous and three heterozygous for the mutant allele). Cats affected by ABCB11930_1931del TC would be expected to have a similar phenotype as dogs with the previously characterized ABCB1‐1Δ mutation.     

The DC-recorded dog electroretinogram in ketamine-medetomidine anaesthesia

A new selective alpha 2-adre-noreceptor agonist, medetomidine hydrochloride was combined with low dosage ketamine hydrochloride and vecuronium bromide for d.c. (direct current) recordings of fast electroretinographic (ERG) components in nine ophthalmoscopically healthy dark adapted dogs. The dogs were tracheally intubated and manually ventilated. They were given full field single flash stimuli of different intensities starting with near b-wave threshold blue light (tests 1-3), followed by white light (tests 4-6) and 30 Hz photopic flicker (test 7). The a- and b-wave amplitudes and flicker responses were measured from the base line. The latencies were measured from the stimulus moment to the highest point of the different waves.Statistical analysis of results gave individual differencies which had a good constancy. This showed that the dogs had an individual ERG profile according to the standardized method. The latencies varied very little as expected, but the amplitudes differed individually and showed a good constancy as seen by reproducibility tests made nine to ten days later on three of the dogs’ ipsilateral eyes. The combination of drugs used in this study was considered suitable for short term (10-12 minutes) stable d.c.–ERG recordings in dogs as the rod and cone responses had higher amplitudes when compared to an identical examination made with other anaesthetic combinations on the same dogs.Involuntary eye movements and other involuntary muscular activity caused by ketamine in dogs were negligible when using medetomidine premedication and was completely absent when using vecuronium.The anaesthetic method described can be recommended for ambulatory ERG recordings in dogs because of the above mentioned advantages.