Search

Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs. Currently, no standard treatment is available, but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs*1395), was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium (RPE). The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD. [ABSTRACT FROM AUTHOR]

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]

Abstract: Objective: Children with Leber congenital amaurosis (LCA) due to CEP290 mutations show characteristic macular preservation. Spectral domain‐optical coherence tomography (SD‐OCT) is a noninvasive technique to investigate retinal structural changes. Loss of integrity of the ellipsoid zone (EZ) on OCT in people with retinal disease has been associated with loss of visual function and is a useful measure of retinal disease progression. We hypothesized that rdAc felines with Cep290 mutation would have a similar pattern of degeneration, with relative central retinal preservation associated with maintenance of the EZ. Procedures: Fundus imaging, confocal scanning laser ophthalmoscopy, and SD‐OCT cross‐sectional imaging was performed on 11 rdAc cats ranging from 6 months to 10 years of age. Images were collected from the area centralis, visual streak, and the mid‐superior and mid‐inferior retina. Receptor plus (REC+, encompassing the entire length of photoreceptors) thicknesses were measured. Regional rates of degeneration were determined by regression analysis and compared using unpaired t‐tests. The EZ was evaluated for the presence, absence, or loss of definition. Results: RdAc cats showed REC+ thinning over time in all regions. The area centralis and visual streak had a slower rate of thinning than the mid‐peripheral retina. There was loss of integrity of the EZ initially in the more peripheral regions, while its integrity was maintained in the area centralis and visual streak at all ages studied. Conclusions: rdAc cats show preservation of the central retina with maintenance of EZ integrity, which recapitulates findings in human patients. [ABSTRACT FROM AUTHOR]

Objective To evaluate prevalence and characteristics of cataracts in the Norwegian Buhund breed 20 years after high reported prevalence of especially pulverulent nuclear cataracts ( PNCs). Animals studied Two hundred and fifty Norwegian Buhund dogs in Norway, Sweden, and Denmark (117 males and 133 females) with previously unknown eye health status were included. Forty-five dogs had multiple examinations (two to six times over a 6-year period). Median age was 4.4 years [0.2-15.2] at first examination and 5.3 years [0.2-15.2] at last examination. Procedures All dogs underwent regular screening for inherited eye diseases. Results At the last observation of each dog, 52.4% were affected by PNC, categorized as minimal (33 of 250 dogs; 13.2%), mild (31 dogs; 12.4%), moderate (38 dogs; 15.2%), or pronounced (29 dogs; 11.6%). Moderate or pronounced changes were only seen in older dogs, and progressive changes were identified in some of the re-examined dogs. Some dogs, free of lenticular changes at early examinations, were affected by PNC at re-examinations. The odds for finding PNC increased with dog's age up to approximately 8 years. Presumably inherited cataracts other than PNC were found in 53 dogs (21.2%) with cortical (17.6%) and posterior polar (6.4%) locations as the most common ones. Conclusions The high prevalence of PNC in the breed reported 20 years ago persists. PNCs are not always visible in young dogs, and the rate of progression varies. The prevalence of other types of cataract is also high, but cataracts rarely cause loss of vision in this breed. [ABSTRACT FROM AUTHOR]

A 10-year-old intact female Jindo dog was presented with a 1-week history of conjunctival redness and ocular discharge in the left eye. There was an absence of menace response, dazzle reflex, and direct pupillary light reflex. Slit-lamp biomicroscopy revealed corneal edema, ciliary flush, and aqueous flare. Intraocular pressure was 68 mmHg. Based on the information available, a diagnosis of glaucoma and uveitis was made. Subsequent histopathologic examination showed the glaucoma was produced by the effects of goniodysgenesis, posterior synechia, and pigment dispersion in the trabecular meshwork. This is the first report of primary glaucoma caused by goniodysgenesis in Jindo dogs. [ABSTRACT FROM AUTHOR]

A 2-year-old intact female Bengal cat was presented with a 6-month history of visual impairment. The cat manifested bilateral negative menace responses and dazzle reflexes and sluggish pupillary light reflexes. Bilateral fundus changes included generalized tapetal hyperreflectivity, advanced retinal vascular attenuation, and increased pallor of the optic disc. A diagnosis of bilateral retinal degeneration was made. The clinical findings suggest that the investigated Bengal cat was most likely to have an inherited retinal degeneration. Further studies of the Bengal cat breed are needed to determine the prevalence of inherited retinal degeneration in this breed in Korea. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The objective of the study was to examine whether a nutritional antioxidant supplementation could improve visual function in healthy dogs as measured by electroretinography (ERG) and autorefraction. A total of twelve Beagles, 6 to 8 years of age, with normal eyes upon indirect ophthalmoscopy and slit lamp biomicroscopy, were age and sex matched and randomly assigned to receive a feeding regimen for 6 months with or without a daily antioxidant supplementation. Portable, mini-Ganzfeld ERG and a Welch Allyn hand-held autorefractor were used to test retinal response and refractive error in the dogs at baseline and at the end of the supplementation period. All ERG a-wave amplitudes obtained were increased in the treatment group compared with those of dogs in the control group, with significant improvements in the scotopic high and photopic single flash cone ERG responses (P < 0·05 for both). For the b-wave amplitudes, all responses were similarly increased, with significant improvements in responses for the scotopic high light intensity stimulation (P < 0·05), and for photopic single flash cone and 30 Hz flicker (P < 0·01 for both) recordings. Change in refractive error was significantly less in the treatment group compared with that of the control group during the 6-month study (P < 0·05). Compared with the control group, the antioxidantsupplemented group showed improvement to varying degrees for retinal function and significantly less decline in refractive error. Dogs, like humans, experience retinal and lens functional decline with age. Antioxidant supplementation as demonstrated may be beneficial and effective in the long-term preservation and improvement of various functions of the canine eye. [ABSTRACT FROM AUTHOR]

The full-field, flash electroretinogram (ERG) is now a widely used test of canine retinal function for the clinical diagnosis of hereditary retinal dystrophies and other causes of retinal degeneration, assessment of retinal function in patients with opaque media, ruling out of generalized retinal diseases in patients with sudden loss of vision and in ophthalmological research, as well as in pharmaceutical and toxicological screening for deleterious side effects of drugs and other chemical compounds. In 2002, the first guidelines for clinical ERGs in this species adopted by the European College of Veterinary Ophthalmologists were published. This work provides an update of these guidelines. [ABSTRACT FROM AUTHOR]

Intensive breeding and selection on desired traits have produced high rates of inherited diseases in dogs. Hereditary retinal degeneration, often called progressive retinal atrophy (PRA), is prevalent in dogs with disease entities comparable to human retinitis pigmentosa (RP) and Leber's congenital amaurosis (LCA). Recent molecular studies in the English Springer Spaniel (ESS) dog have shown that PRA cases are often homozygous for a mutation in the RPGRIP1 gene, the defect also causing human RP, LCA, and cone rod dystrophies. The present study characterizes the disease in a group of affected ESS in USA, using clinical, functional, and morphological studies. An objective evaluation of retinal function using electroretinography (ERG) is further performed in a masked fashion in a group of American ESS dogs, with the examiner masked to the genetic status of the dogs. Only 4 of 6 homozygous animals showed clinical signs of disease, emphasizing the need and importance for more precise studies on the clinical expression of molecular defects before utilizing animal models for translational research, such as when using stem cells for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Only in recent years have specific mutations been elucidated for feline hereditary retinal dystrophies. Molecular genetic characterization of feline diseases has so far been a slow process but with a full genome sequence for the cat recently completed and the development of a feline single nucleotide polymorphism chip, the characterization of feline monogenic disorders will be significantly simplified. This review summarizes current knowledge with regard to specific hereditary retinal dystrophies in cats and gives an overview of how cats can be used as models in translational research. [ABSTRACT FROM AUTHOR]

Objective To perform electroretinography on normal anesthetized western gray kangaroos ( Macropus fuliginosus). Animals studied Six captive western gray kangaroos. Procedures The kangaroos were anesthetized using a combination of ketamine and medetomidine via a remote drug delivery system, then were maintained on isoflurane after endotracheal intubation and reversal of the medetomidine with atipamazole. After a minimum of 20 min of dark adaptation, electroretinograms were obtained using a handheld electroretinography (ERG) machine using a single flash protocol at three light intensities: 10 mcd.s/m2, 3000 mcd.s/m2, 10 000 mcd.s/m2. Results At 10 mcd.s/m2 the mean b-wave amplitude and implicit time was 102.0 μV (SD ± 41.3 and 95% CI 68.9–135.1) and 78.4 ms (SD ± 8.3 and 95% CI 71.8–85.0). At 3000 mcd.s/m2 the mean a-wave amplitude and implicit time was 69.9 μV (SD ± 20.5 and 95% CI 53.5–86.3) and 17.6 ms (SD ± 1.5 and 95% CI 16.4–18.8) and the mean b-wave amplitude and implicit time was 175.4 μV (SD ± 35.9 and 95% CI 146.7–204.1) and 74.1 ms (SD ± 3.5 and 95% CI 71.2–76.9). At 10 000 mcd.s/m2 the mean a-wave amplitude and implicit time was 89.1 μV (SD ± 27.1 and 95% CI 67.5–110.8) and 16.8 ms (SD ± 1.0 and 95% CI 16.0–17.0) and the mean b-wave amplitude and implicit time was 203.7 μV (SD ± 41.4 and 95% CI 170.6–236.8) and 75.4 ms (SD ± 3.3 and 95% CI 72.8–78.1). Conclusion Electroretinography outside of the typical clinical setting is feasible using a portable ERG system and allows for quick analysis of retinal function in exotic species. [ABSTRACT FROM AUTHOR]

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]

Purpose To determine the effects of a standardized intravenous dose of an α-2 agonist (Domitor®, Orion Pharma, distributed by Pfizer Animal Health, Exton, PA) on the electroretinogram (ERG) response in normal dogs. Methods Twenty-five normal dogs were used to collect ERG responses including a- and b-wave implicit times (IT) and amplitudes (AMP) before and after administration of medetomidine. Dogs were dark adapted for 20 min and ERGs were obtained using the HMsERG (RetVetCorp Inc., Columbia, MO). The QuickRetCheck protocol (Narfström) was employed to provide the following flash intensities: 10 mcd s/m2, 3 cd s/m2, and 10 cd s/m2. ERGs were repeated after 375 µg/m2 of medetomidine intravenously. Statistical analysis of the difference between the responses before and after medetomidine at all flash intensities was performed using a mixed effects model foranova. Results The P value for the effect of medetomidine on each of the ERG responses was < 0.01. The estimates of the effect of medetomidine were (+)1.35 ms, (–)23 µV, (+)3.16 ms, and (–)47 µV for the a-wave IT, a-wave AMP, b-wave IT, and the b-wave AMP, respectively. Conclusions Medetomidine significantly prolongs the implicit time and lowers the amplitude response of both the a- and b-waves in normal dogs at all flash intensities examined. Clinically, however, medetomidine only minimally affects the retinal responses and is a viable choice for use in dog ERGs. [ABSTRACT FROM AUTHOR]

The author reflects on the importance of subretinal implantation to restore the dying photoreceptors of the visually impaired patients. She asserts that the research on the implantation carefully studied not on the normal function and health of the eyes, but also on the cognitive processing of the brain. She further discusses that there are six research teams including the Association for Research in Vision and Ophthalmology (ARVO) who developed the innovative methods for the eye surgery.

A mutation in the CEP290 gene is reported in a cat pedigree segregating for autosomal recessive (AR) late-onset photoreceptor degeneration (rdAc). An initial screen of 39 candidate genes and genomic locations failed to detect linkage to cat rdAc. Linkage was ultimately established on cat B4 with 15 simple tandem repeat markers (logarithm of odds [LOD] range 4.83-15.53, Θ = 0.0), in a region demonstrating conserved synteny to human chromosome 12, 84.9-90.63 Mb. The sequence of 10 genes with feline retinal expression was examined in affected and unaffected individuals. A single-nucleotide polymorphism was characterized in intron 50 of CEP290 (IVS50 + 9T>G) that creates a strong canonical splice donor site, resulting in a 4-bp insertion and frameshift in the mRNA transcript, with subsequent introduction of a stop codon and premature truncation of the protein. A population genetic survey of 136 cats demonstrated that the rdAc mutation is in low frequency in Abyssinian populations (0.13, Sweden; 0.07, United States) and absent in breeds of non-Abyssinian heritage. Mutations in CEP290 have recently been shown to cause two human diseases,Joubert syndrome, a syndromic retinal degeneration, and Leber's congenital amaurosis, an AR early-onset retinal dystrophy. Human AR retinitis pigmentosa is among the most common causes of retinal degeneration and blindness, with no therapeutic intervention available. This identification of a large animal model for human retinal blindness offers considerable promise in developing gene-based therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

These procedures described for the dog ERG were approved at the 1st European Conference on Veterinary Visual Electrophysiology in Vienna, Austria, May 30, 2000. Dr. Narfström was Chair of the Committee for a Harmonized ERG Protocol, appointed by the European College of Veterinary Ophthalmology (ECVO), and Dr. Ofri was secretary. The other coauthors are committee members. Guidelines for ERG procedures in other animal species for clinical and laboratory studies are planned for in the future and the present guidelines are planned to be revised on a biannual basis. A brief report of the recommended procedures is available in the Conference Proceedings book. [ABSTRACT FROM AUTHOR]

Abstract Previous studies using electroretinography and immunohistochemistry have shown normal cone function and structure in early stages of hereditary rod-cone degeneration of Abyssinian cats. To further investigate the cone photoreceptors and the inner retina of dystrophic cats, antibodies against green- and blue-sensitive cones and specific cell types of inner retina were used in seven cats with the recessively inherited rod-cone degeneration, and three normal European short-haired cats. There was a reduction in number of both types of cones early in the disease. Changes at early stages of disease also occurred among horizontal cells in which there was an extension and a thickening of their lateral processes. The regular configuration of bipolar cells was changed in the more advanced stages of disease and their apical dendrites were lost. Abnormalities were not observed in the amacrine cells and in the ganglion cell layer in any of the present cases. This study shows that the cone system is morphologically abnormal in young cats at an earlier stage of disease than previously shown. The present findings also support the assumption that the inner retina is largely preserved throughout the disease process. [ABSTRACT FROM AUTHOR]

Introduction: Multifocal electroretinography (MF-ERG) is widely used in the detection of local retinal dysfunction. However, the position of the stimulus on the retina and the stability of fixation are usually not directly accessible. Thus, devices have been designed for a continuous fundus visualization during recording. Methods: MF-ERGs were recorded with a RetiScanTM system connected to two different Scanning-laser ophthalmoscopes (SLOs) that use either a red (633 nm) or green (415 nm) laser for stimulation, and a VERISTM 4 system connected to a piggyback stimulator prototype that added the stimulus to the optical pathway of the SLO by means of a wavelength-sensitive mirror. Fundus visualization was achieved with the infrared lasers of the SLOs (780 and 835 nm). Results: The most extensive study so far with a green laser stimulus in a cat model of retinal degeneration demonstrated the capability of the device to detect retinal landmarks and the different stages of degeneration. Also, the advantages of exactly reproducible stimulus positioning for averaging within and comparison between disease groups became apparent. The results with the same setup in transgenic mice suggest a pure cone origin of the responses. In humans, recordings show that fixation is sufficiently good in most subjects. It is not clear yet whether red or green laser stimulation (or both) is preferable. The results with the prototype were very similar to the MF-ERGs obtained with a standard CRT screen. Conclusions: All three devices allowed us to record MF-ERGs with continuous fundus monitoring. Although further refinements are necessary, it is obvious that fundus controlled methods will improve the reliability of MF-ERG in future research on glaucoma, transplantation studies, and evaluation of gene therapy. [ABSTRACT FROM AUTHOR]

Light-adapted cone ERG in response to white stimuli with long duration (200 ms) was studied in seven normal cats and six cats with early to moderate, inherited retinal dystrophy. The stimuli typically elicited an ERG consisting of an a- and b-wave in response to light onset, whereas light-offset was followed by a cornea-positive d-wave and subsequent negative dip and occasionally a second positive peak in both normal and dystrophic cats, although b- and d- waves had less distinct peaks in cats with moderately advanced retinal dystrophy. Linear regression models indicated a positive correlation between d-wave amplitude and stimulus luminance, whereas a negative correlation was found between amplitude and background light luminance in normal cats. The d-wave implicit time was independent of both stimulus and background light luminance in normal cats. The d-wave amplitude was not significantly different in dystrophic cats, whereas the implicit time was increased when affected cats were compared to normal cats. The significant increase in implicit time in dystrophic cats could not be explained with a reduced sensitivity of the off-pathway to background or stimulus light. This is supported by the finding that d-wave amplitude was not significantly altered in early to moderately advanced dystrophic cats. [ABSTRACT FROM AUTHOR]

Levels of interphotoreceptor retinoid-binding protein (IRBP) protein and message in retinas of Abyssinian cats homozygous for progressive rod-cone degeneration were determined at early ages, well before the onset of clinical retinal degeneration. IRBP gene expression was assessed by immunochemical quantitation of IRBP protein, and by Northern blotting and slot-blotting of total RNA using a human IRBP cDNA probe. Morphology was assessed by electron microscopy and immunocytochemistry. Levels of both IRBP protein and message in affected Abyssinian cat retinas were significantly reduced below normal as early as 4 weeks of age at the earliest stage of retinal disorientation. Opsin mRNA was more abundant in affected Abyssininian cat retinas than in control retinas. This was at least 1 year before the onset of clinical symptoms. The reduction in IRBP gene expression to levels significantly below normal well before the onset of retinal degeneration in affected Abyssinian cat retinas indicates that this represents a primary defect or at least an early problem that could itself cause adverse effects. [ABSTRACT FROM AUTHOR]

Retinae of Abyssinian cats homozygous for a retinal degeneration gene, and normal controls, have been investigated using antibodies directed against opsin, transducin α (TD-α), S-antigen (48K protein), interphotoreceptor retinoid-binding protein (IRBP), and cone outer segments. IRBP-immunoreactivity (IR) is much reduced at stage 2 of the disease in affected retinae; later massive photoreceptor cell death occurs. In cats, at a late stage of the disease, the retina exhibits few S-antigen-IR cells in the peripheral part of the retina whereas, in the central part, some patches of cells exhibiting opsin-IR, TD-α-IR, and S-antigen-IR are present in remnants of the outer nuclear layer (ONL). No IRBP-IR is detectable at this stage. The form and size of the majority of these remaining cells, however, does not resemble that of normal photoreceptors. No, or only rudimentary, inner and outer segments are present; long bifurcating basal protrusions often occur. These cells, which could be remains of cone elements, are S-antigen immunoreactive. Double labelling for different retina-specific proteins reveals a co-localization of opsin, TD-α and S-antigen in some, but not all, remaining photoreceptor elements. Cells exhibiting opsin-IR also show TD-α-IR and S-antigen-IR located within the entire cell and its protrusions. In control retinae and retinae at early stages of the disease, immunoreactions are comparable with all antibodies used. However, TD-α-IR is less intensive in the photoreceptor terminals. S-antigen-IR cones are most frequently present in the peripheral retina. Reduction of IRBP at an early stage of the disease could be one of the factors leading to photoreceptor cell death at later stages. [ABSTRACT FROM AUTHOR]