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Objectives: The purpose of this study was to investigate the prevalence of cataracts in the Russian Blue breed of cats in Sweden, and to describe the clinical appearance of this presumed inherited form of cataract., Methods: A total of 66 Russian Blue cats were examined in Sweden, between March and October 2014, using standard examination techniques. The examined cats were between 3 months and 14 years of age. Pedigrees were collected from all examined cats for genetic studies., Results: Mild-to-severe forms of mainly bilateral cataracts were observed in 22/66 examined Russian Blue cats of both sexes. Two affected cats were <1 year of age. The most frequently observed appearance of a cataract was a small triangular, Y-shaped or circular opacity at the border of the posterior nucleus and the anterior part of the posterior cortex, which caused no observable visual impairment. More extended forms were observed in 6/22 cats, with involvement of both the nucleus and either the entire cortex or parts of the posterior and/or anterior cortex. Visual impairment or blindness was observed in the latter six cases. Pedigree analyses indicated a simple autosomal recessive mode of inheritance for the defect, although a dominant mode with incomplete penetrance could not be excluded., Conclusions and Relevance: This study indicates that the Russian Blue breed of cat is affected by hereditary cataracts. The high prevalence in young cats and the characteristic location of the most frequently observed defect in the study suggest an early onset type of cataract. The breeders should be aware of this defect and have their cats examined by a veterinary ophthalmologist before breeding of an individual Russian Blue cat is considered.

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., (© 2017 American College of Veterinary Ophthalmologists.)

Over 200 hereditary diseases have been identified and reported in the cat, several of which affect the eye, with homology to human hereditary disease. Compared with traditional murine models, the cat demonstrates more features in common with humans, including many anatomic and physiologic similarities, longer life span, increased size, and a genetically more heterogeneous background. The development of genomic resources in the cat has facilitated mapping and further characterization of feline models. During recent years, the wealth of knowledge in feline ophthalmology and neurophysiology has been extended to include new diseases of significant interest for comparative ophthalmology. This makes the cat an extremely valuable animal species to utilize for further research into disease processes affecting both cats and humans. This is especially true in the advancement and study of new treatment regimens and for extended therapeutic trials. Groups of feline eye diseases reviewed in the following are lysosomal storage disorders, congenital glaucoma, and neuroretinal degenerations. Each has important implications for human ophthalmic research.

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., (© 2011 American College of Veterinary Ophthalmologists.)

Purpose: To elucidate the gene defect in a pedigree of cats segregating for autosomal dominant rod-cone dysplasia (Rdy), a retinopathy characterized extensively from a clinical perspective. Disease expression in Rdy cats is comparable to that in young patients with congenital blindness (Leber congenital amaurosis [LCA] or retinitis pigmentosa [RP])., Methods: A pedigree segregating for Rdy was generated and phenotyped by clinical ophthalmic examination methods including ophthalmoscopy and full-field flash electroretinography. Short tandem repeat loci tightly linked to candidate genes for autosomal dominant retinitis pigmentosa in humans were genotyped in the pedigree., Results: Significant linkage was established to the candidate gene CRX (LOD = 5.56, = 0) on cat chromosome E2. A single base pair deletion was identified in exon 4 (n.546delC) in affected individuals but not in unaffected littermates. This mutation generates a frame shift in the transcript, introducing a premature stop codon truncating the putative CRX peptide, which would eliminate the critical transcriptional activation region. Clinical observations corroborate previously reported clinical reports about Rdy. Results show that the cone photoreceptor system was more severely affected than the rods in the early disease process., Conclusions: A putative mutation causative of the Rdy phenotype has been described as a single base pair deletion in exon 4 of the CRX gene, thus identifying the first animal model for CRX-linked disease that closely resembles the human disease. As such, it will provide valuable insights into the mechanisms underlying these diseases and their variable presentation, as well as providing a suitable model for testing therapies for these diseases.

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.

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.

Aim: To evaluate two recent methods for detecting feline hereditary rod cone degeneration with maximum efficiency from a long full-field flash ERG protocol. One combines 12 of these measures in an equation that is derived from iterative principal components factor analysis. The other uses the amplitude of the a-wave to the brightest available flash alone., Methods: We tested the original 12-parameter equation, by applying it to 50 new ERG series in 23 backcrossed cats. They were necessarily either heterozygous or homozygous for hereditary rod cone degeneration. A masked observer compared the ERG score and fundus examinations. We reanalyzed the old, new and combined data sets. Data sets with only one session per animal were analysed to avoid problems from non-random sampling. A two factor linear model of the a-wave was evaluated., Results: The prior equation, applied to the new data, discriminated the groups as well as it had initially. In the reanalysis, group separation continued to increase with even fewer measures compared to the previously reported study. Eventually, one measure, the amplitude of the a-wave (amax) to the brightest scotopic flash (Imax) discriminated the groups better than any other measure or combination of measures in all analyses, including data sets using only one session for each animal and in a two factor linear model of the a-wave., Conclusion: Amax to Imax alone proved to be the best diagnostic criterion in all analyses. No linear model is likely to discriminate affected from unaffected animals more effectively because additional variables increased variance more rapidly than they increased discrimination. Amax to Imax may detect other rod and rod/cone dystrophies equally efficiently.

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 15.5 microm 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.

Glaucoma and inherited retinal degeneration/dystrophy are leading causes of blindness in veterinary patients. Currently, there is no treatment for the loss of vision that characterizes both groups of diseases. However, this reality may soon change as recent advances in understanding of the disease processes allow researchers to develop new therapies aimed at preventing blindness and restoring vision to blind patients. Elucidating the molecular mechanisms of retinal ganglion cell death in glaucoma patients has led to the development of neuroprotective drugs which protect retinal cells and their function from the disastrous effects of elevated pressure. Identification of the genetic mutation responsible for inherited degenerations and dystrophies of the outer retina has enabled researchers using gene therapy to restore vision to blind dogs. Other patients may benefit from retinal transplantation, stem cell therapy, neuroprotective drugs, nutritional supplementation and even retinal prostheses. It is possible that soon it will be possible to restore sight to some blind patients.

Objective: To characterize the effects of oral administration of a high dose of enrofloxacin to cats., Animals: 24 (12 male and 12 female) young healthy cats., Procedures: Cats were allocated on the basis of sex into 2 groups (4 males and 4 females/ group) from which 3 subgroups for 3 durations (3, 5, or 7 days) of enrofloxacin (50 mg/kg, PO, q 24 h) or control solution (1 mL of water, PO, q 24 h) administration that began on day -1 were created. Funduscopic examinations were performed daily. Electroretinography (ERG) was performed before and every 2 to 3 days after the start of oral administration. Four cats/study group were euthanized on days 3, 5, and 7, and eyes were collected for light and electron microscopic evaluations., Results: Neurologic, funduscopic, and ERG abnormalities were evident only in cats administered enrofloxacin. Funduscopic changes (granular appearance or graying of the area centralis) were noticed on or before day 3 (after only 3 days of enrofloxacin administration), with subsequent similar changes along the visual streak. Vascular attenuation (between days 2 and 4) and generalized tapetal hyperreflectivity (between days 5 and 7) followed. Reduction in b-wave ERG amplitude preceded funduscopic changes. Morphologic changes in the photoreceptor layers correlated with duration of enrofloxacin administration, with generalized degenerative changes evident after 3 doses., Conclusions and Clinical Relevance: The study indicated that a high dose of enrofloxacin (50 mg/kg/d, PO) induced retinal and systemic changes. Enrofloxacin at 10 times the recommended dosage is acutely toxic to the outer retina of clinically normal cats.

Purpose: To investigate the effects of a hereditary retinal degeneration on retinal oxygenation and determine whether it is responsible for the severe attenuation of retinal circulation in hereditary photoreceptor degenerations., Methods: Seven adult Abyssinian cats affected by hereditary retinal degeneration were studied. Oxygen microelectrodes were used to collect spatial profiles of retinal oxygenation in anesthetized animals. A one-dimensional model of oxygen diffusion was fitted to the data to quantify photoreceptor oxygen utilization (Qo(2))., Results: Photoreceptor Qo(2) progressively decreased until it reached zero in the end stage of the disease. Average inner retinal oxygen tension remained within normal limits at all disease stages, despite the observed progressive retinal vessel attenuation. Light affected photoreceptors normally, decreasing Qo(2) by approximately 50% at all stages of the disease., Conclusions: Loss of photoreceptor metabolism allows choroidal oxygen to reach the inner retina, attenuating the retinal circulation in this animal model of retinitis pigmentosa (RP) and probably also in human RP. As the degeneration progresses, there is a strong relationship between changes in the a-wave of the ERG and changes in rod oxidative metabolism, indicating that these two functional measures change together.

Purpose: To examine phototransduction using the a-wave and other aspects of retinal function with the intraretinal b- and c-waves at different stages of an inherited photoreceptor degeneration in Abyssinian cats., Methods: Vitreal and intraretinal ERGs were recorded from eight dark-adapted, anesthetized Abyssinian cats. Brief bright flashes were used to elicit vitreal a- and b-waves. Longer, weaker flashes were used to elicit intraretinal b- and c-waves. Stages 1 through 4 of the disease were characterized ophthalmoscopically. Parameters of the Lamb and Pugh a-wave model (a(max), A, and t(eff)) for the Abyssinian cats were compared with those for normal cats. Light microscopy was used to count photoreceptor nuclei., Results: The maximum a-wave amplitude, a(max), was significantly smaller in stage 1, and continued to decrease (stage 1: 50% of normal, stage 2: 28%, stage 3: 27%; and stage 4: unrecordable). There was a small, but not significant, decrease in the amplification constant A from 0.24 +/- 0.11 s(-2) in normal cats to 0.16 +/- 0.08 s(-2) in Abyssinian cats. The intraretinal b- and c-wave amplitudes decreased most dramatically during the early stage of the disease. Affected animals had fewer photoreceptors than unaffected Abyssinians or control animals. The number of photoreceptors declined most rapidly in the inferior periphery., Conclusions: The amplitudes of all ERG components were already reduced significantly by stage 1 and progressively declined. The lack of major changes in a-wave model parameters indicates that the degeneration is probably not due to a mutation in transduction proteins. Losses of photoreceptor function were larger than losses of photoreceptor nuclei.

Objective: To develop a method to electrophysiologically differentiate heterozygous-carrier Abyssinian-crossbred cats from homozygous-affected Abyssinian-crossbred cats before clinical onset of inherited rod-cone retinal degeneration., Animals: 14 back-crossed Abyssinian-crossbred cats of unknown genotype (homozygous or heterozygous) for inherited rod-cone retinal degeneration, 24 age-matched mixed-breed control cats, 6 age-matched heterozygous Abyssinian-crossbred cats, and 6 homozygous Abyssinian cats., Procedure: Electroretinography (ERG) of heterozygous and homozygous cats revealed differences, especially for scotopic recordings. Frequent ophthalmoscopy and ERG (2 to 5 times; at intervals of 3 to 6 months) of back-crossed cats were performed. Amplitudes and implicit times were analyzed by use of a graphic representation of results. Ratios for amplitudes of the b-waves to amplitudes of the a-waves (b-wave:a-wave) were compared., Results: 8 back-crossed cats had decreased a-wave amplitudes, increased b-wave implicit times, and abnormal ERG waveforms. Values for the b-wave:a-wave for the highest scotopic light intensity were significantly higher for those same 8 cats., Conclusions and Clinical Relevance: The 8 back-crossed Abyssinian-crossbred cats with abnormal results developed fundus changes over time consistent with disease. A graphic representation of ERG results can be used to differentiate between genotypes prior to funduscopic changes. Values for the b-wave:a-wave ratio provide confirmation. These ERG analyses may be applied clinically in the diagnosis of retinal degenerations in various species., Impact for Human Medicine: Cats with hereditary rod-cone degeneration may be a useful model for comparative studies in relation to retinitis pigmentosa in humans. Similar evaluations of ERG results could possibly be used for humans with suspected generalized retinal degeneration.

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 alpha-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.

Aim: To determine the diagnostic efficiency of scores in a long protocol ectroretinogram (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 > or = 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 at testing., 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.

Purpose: To study retinal function in cats homozygous and heterozygous for a recessively inherited rod-cone degeneration., Methods: 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., Results: 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., Conclusions: 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.

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 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]