RESUMO
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 (âprcdâ)-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.
Assuntos
Doenças do Cão/genética , Doenças Retinianas/veterinária , Animais , Estudos de Casos e Controles , Doenças do Cão/patologia , Cães , Feminino , Predisposição Genética para Doença , Masculino , Doenças Retinianas/genéticaRESUMO
Volume homeostasis is essential for the preservation of lens transparency and this is of particular significance to anadromous fish species where migration from freshwater to seawater presents severe osmotic challenges. In Atlantic salmon (Salmo salar L.), aqueous humor (AH) osmolality is greater in fish acclimated to seawater compared with young freshwater fish, and levels of lens N-acetylhistidine (NAH) are much higher in seawater fish. Here we investigate NAH as an osmolyte in the lenses of salmon receiving diets either with or without histidine supplementation. In the histidine-supplemented diet (HD) histidine content was 14.2 g/kg, and in the control diet (CD) histidine content was 8.9 g/kg. A transient increase in AH osmolality of 20 mmol/kg was observed in fish transferred from freshwater to seawater. In a lens culture model, temporary decreases in volume and transparency were observed when lenses were exposed to hyperosmotic conditions. A positive linear relationship between extracellular osmolality and lens NAH content was also observed, whereas there was no change in lens histidine content. Hypoosmotic exposure stimulated [(14)C]-histidine efflux by 9.2- and 2.6-fold in CD and HD lenses, respectively. NAH efflux, measured by HPLC, was stimulated by hypoosmotic exposure to a much greater extent in HD lenses. In vivo, lens NAH increased in response to elevated AH osmolality in HD but not CD fish. In conclusion, NAH has an important and novel role as a compatible osmolyte in salmon lens. Furthermore, it is the major osmolyte that balances increases in AH osmolality when fish move from freshwater to seawater. A deficiency in NAH would lead to a dysfunction of the normal osmoregulatory processes in the lens, and we propose that this would contribute to cataract formation in fish deficient in histidine.
Assuntos
Histidina/análogos & derivados , Cristalino/química , Salmo salar/metabolismo , Animais , Humor Aquoso/química , Humor Aquoso/metabolismo , Cromatografia Líquida de Alta Pressão , Histidina/química , Histidina/metabolismo , Potenciais da Membrana/fisiologia , Técnicas de Cultura de Órgãos , Concentração Osmolar , Água do Mar , Espectrofotometria UltravioletaRESUMO
PURPOSE: To describe and classify the morphologic changes in a naturally occurring dog model of early-onset cone-rod dystrophy (CRD) and to correlate these with earlier described clinical characteristics of the disease in dogs. METHODS: Purpose-bred Standard Wire-Haired Dachshunds (SWHDs) derived from a large pedigree of dogs with early-onset CRD were euthanatized at defined ages to characterize morphologic changes in the disease process. Specimens were examined by light microscopy, including morphometric studies, electron microscopy, and immunohistochemistry. Peanut agglutinin (PNA), protein kinase C (PKC), synaptophysin (Syn), rhodopsin (Rho)-63, glial fibrillary acidic protein (GFAP), and short-wavelength cone opsin (OS) were used for immunohistochemical characterization. RESULTS: The photopic cone-system-derived ERG amplitudes were already significantly reduced or nonrecordable in CRD-affected dogs at 5 weeks, the earliest age studied. The outer retina was morphologically most severely affected initially, with a subsequent degeneration of the inner retina. Cone degeneration was more pronounced than rod degeneration in young CRD-affected dogs. There was a marked phenotypic variation based on morphologic findings in the affected dogs. At the earliest time point studied (5-8 weeks) cone photoreceptor and glial cell abnormalities were observed, in accordance with earlier studies based on electrophysiological and clinical findings in which day blindness and abnormal cone ERGs were observed in young affected SWHD puppies. Preliminary genetic studies have indicated an autosomal recessive mode of inheritance for the defect. CONCLUSIONS: Through functional and structural characterization, early-onset cone abnormalities were found, consistent with a cone dysplasia at an age when rod structure was normal. Further studies are in progress to identify the gene(s) involved in this retinal disease process. The presently described natural animal model of primary cone dysplasia followed by rod degeneration may provide further insight into the human counterpart. Further studies are needed to ascertain an autosomal recessive mode of inheritance for CRD in the SWHD.
Assuntos
Doenças do Cão/fisiopatologia , Eletrorretinografia/veterinária , Células Fotorreceptoras de Vertebrados , Retina/fisiopatologia , Retina/ultraestrutura , Degeneração Retiniana/veterinária , Animais , Modelos Animais de Doenças , Doenças do Cão/metabolismo , Cães , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Microscopia Eletrônica , Linhagem , Fenótipo , Células Fotorreceptoras de Vertebrados/fisiologia , Células Fotorreceptoras de Vertebrados/ultraestrutura , Proteína Quinase C/metabolismo , Retina/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/fisiopatologia , Rodopsina/metabolismo , Opsinas de Bastonetes/metabolismo , Sinaptofisina/metabolismoRESUMO
BACKGROUND: A genetic study was performed to identify candidate genes associated with day blindness in the standard wire haired dachshund. Based on a literature review of diseases in dogs and human with phenotypes similar to day blindness, ten genes were selected and evaluated as potential candidate genes associated with day blindness in the breed. RESULTS: Three of the genes, CNGB3, CNGA3 and GNAT2, involved in cone degeneration and seven genes and loci, ABCA4, RDH5, CORD8, CORD9, RPGRIP1, GUCY2D and CRX, reported to be involved in cone-rod dystrophies were studied. Polymorphic markers at each of the candidate loci were studied in a family with 36 informative offspring. The study revealed a high frequency of recombinations between the candidate marker alleles and the disease. CONCLUSION: Since all of the markers were at the exact position of the candidate loci, and several recombinations were detected for each of the loci, all ten genes were excluded as causal for this canine, early onset cone-rod dystrophy. The described markers may, however, be useful to screen other canine resource families segregating eye diseases for association to the ten genes.
Assuntos
Doenças do Cão/genética , Transtornos da Visão/veterinária , Animais , Cães , Feminino , Genótipo , Masculino , Repetições de Microssatélites/genética , Linhagem , Recombinação Genética , Transtornos da Visão/genéticaRESUMO
Osmotic cataracts were diagnosed in all of 191 Atlantic salmon Salmo salar L. postsmolts caught during 8 trawl hauls on the western side of the Vøringsplateau, Norwegian Sea, in June 2001. The changes varied from a hazy opacity in the anterior part of the lens to cataracts affecting the whole lens. Severely affected lenses appeared swollen and large vacuoles were visible in the opaque areas. Large vacuoles in otherwise clear lenses were diagnosed in 1 of 4 adult salmon examined. Histologically, widened sutures, vacuolation of lens epithelium and cortex, and proteinaceous lakes subjacent to the epithelium were the most frequent changes, while extensive cortical necroses and epithelial proliferation were seen in a few cases. UV-absorbance of the aqueous humor was determined and levels compared to plasma levels and also to levels in farmed Atlantic salmon of the same developmental stage. Wild salmon generally showed higher levels of protective factors than farmed fish. The osmotic type of cataract diagnosed leads to poor vision and is a potential cause of reduced survival in postsmolts. The cause of the cataracts could not be determined, but defective osmoregulation is suspected.
Assuntos
Catarata/veterinária , Doenças dos Peixes/diagnóstico , Cristalino/patologia , Salmo salar , Animais , Catarata/diagnóstico , Catarata/epidemiologia , Catarata/patologia , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/patologia , Cristalino/efeitos da radiação , Cristalino/ultraestrutura , Noruega , Raios Ultravioleta/efeitos adversos , Equilíbrio HidroeletrolíticoAssuntos
Oftalmopatias Hereditárias/terapia , Oftalmopatias Hereditárias/veterinária , Glaucoma/terapia , Glaucoma/veterinária , Animais , Doenças do Gato/patologia , Doenças do Gato/terapia , Gatos , Doenças do Cão/patologia , Doenças do Cão/terapia , Cães , Oftalmopatias Hereditárias/patologia , Glaucoma/patologiaRESUMO
Cone-rod dystrophy is a retinal degenerative disorder occurring naturally in man and dog. Here we identify a novel gene for early-onset cone-rod dystrophy in the wire-haired dachshund. For the first time, we use genome-wide association-based Sibling Transmission Disequilibrium Test (sibTDT) analysis of only 13 discordant sib-pairs to identify a single significantly associated 6.5-Mb region (PrawTDT = 4.8 x 10(-5), PgenomeTDT = 6 x 10(-4)) on canine chromosome 5, containing more than 70 genes. Segregation studies using microsatellites in the candidate region including additional meiosis supported the sibTDT analysis but could not further reduce the area. Candidate gene resequencing identified a 180-bp deletion in exon/intron 5 of NPHP4 (nephronophthisis 4, also known as nephroretinin). RT-PCR analysis of NPHP4 in cases and controls showed exon skipping of exon 5, resulting in a truncated protein that retains the binding domain interacting with nephronophthisis 1 (also known as nephrocystin-1) in the kidney but lacks the domain interacting with RPGRIP1 in retina. We suggest that this deletion in the canine NPHP4 gene is the cause of cone-rod dystrophy in the standard wire-haired dachshund. In humans, mutations in NPHP4 have been associated with simultaneous eye and kidney disease. Here we describe the first naturally occurring mutation in NPHP4 without additional kidney disease. Further studies will permit elucidation of the complex molecular mechanism of this retinopathy and the development of potential therapies.
Assuntos
Doenças do Cão/genética , Deleção de Genes , Retinose Pigmentar/veterinária , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise Mutacional de DNA , Cães , Genes Recessivos , Repetições de Microssatélites , Dados de Sequência Molecular , Mutação , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Retinose Pigmentar/genética , Domínios de Homologia de srcRESUMO
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.
Assuntos
Doenças do Cão/diagnóstico , Predisposição Genética para Doença , Retinose Pigmentar/veterinária , Animais , Animais Recém-Nascidos , Técnicas de Diagnóstico Oftalmológico/veterinária , Doenças do Cão/genética , Doenças do Cão/patologia , Cães , Eletrorretinografia/veterinária , Feminino , Masculino , Linhagem , Retinose Pigmentar/diagnósticoRESUMO
PURPOSE: To describe electroretinographic (ERG) findings in a strain of Standard Wire Haired Dachshund (SWHD)-derived dogs at the ages of approximately 5, 8 and 52 weeks selected for inherited early onset cone-rod dystrophy. METHODS: Nineteen affected and 13 age-matched control SWHDs were included in the study. All dogs were subjected to standardized bilateral Ganzfeld ERGs and ophthalmoscopic examinations at regular intervals. RESULTS: Photopic cone-derived ERG amplitudes were significantly lower and never reached similar levels as those recorded in control dogs. In affected dogs there was no increase with age in amplitudes recorded using 30.1 and 50.1 Hz flicker stimuli. In contrast, in the control groups the photopic b-wave amplitude recorded at 50.1 Hz increased significantly from age 5 to 8 and from 5 to 52 weeks. In affected animals, scotopic rod-derived amplitudes were significantly lower for most recordings compared to those of control dogs, although they increased significantly from age 5 to 8 weeks in both affected and controls. Both a- and b-wave implicit times were significantly longer in the youngest affected group when compared to the age-matched control group at 0.6 log cd s/m(2) and 5.1 Hz single flash light stimuli. In the control dogs, however, there was a significant shortening in a-wave implicit times from age 5 to 8 weeks, and in a- and b-wave implicit times recorded at 5.1 Hz single flash stimuli from age 5 to 52 weeks. CONCLUSIONS: The described retinal degeneration in the SWHD is an early onset cone-rod dystrophy, initially affecting the cone system most severely. Early functional changes are seen in the rod system as well. Inner retina also appears affected already at a young age with findings indicating postsynaptic functional changes already at the earliest time point studied, at age 5 weeks. The present study further indicates that the canine retina reaches maturity later than previously reported, or that there exist major breed differences.
Assuntos
Doenças do Cão/fisiopatologia , Eletrorretinografia/veterinária , Predisposição Genética para Doença , Células Fotorreceptoras Retinianas Cones/fisiopatologia , Displasia Retiniana/veterinária , Células Fotorreceptoras Retinianas Bastonetes/fisiopatologia , Animais , Doenças do Cão/genética , Cães , Células Fotorreceptoras Retinianas Cones/patologia , Displasia Retiniana/genética , Displasia Retiniana/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/patologiaRESUMO
OBJECTIVE: The aim of the study was to evaluate if tonometry and gonioscopy could serve as predictors of later glaucoma development in the English Springer Spaniel, a breed prone to developing primary glaucoma. ANIMALS STUDIED: Gonioscopy was performed on 279 English Springer Spaniel dogs, 119 males and 160 females, with clinically normal eyes. In addition, 14 dogs, five males and nine females were examined for glaucoma. RESULTS: A positive relation between pectinate ligament dysplasia (PLD) and narrowing of the relative width of the ciliary cleft (RWOCC) and also between PLD, RWOCC and age was demonstrated. The prevalence of PLD was 25.5%, which is higher than in other breeds reported. A positive association was demonstrated between PLD and glaucoma, as well as between narrowing of the RWOCC and glaucoma. Glaucoma was not observed in dogs with normal appearance of the iridocorneal angle. English Springer Spaniels related to dogs with glaucoma show more narrowing of the RWOCC and more PLD than unrelated dogs. CONCLUSION: This study demonstrates the positive association between PLD and glaucoma, between narrowing of the iridocorneal angle and glaucoma and the effect of age on the iridocorneal angle. Mating of dogs with normal iridocorneal angles appears to reduce the presence and degree of abnormal appearance of the iridocorneal angle in the offspring. However, breeding only dogs with normal iridocorneal angles without consideration of their relationship to dogs with glaucoma is not a guarantee for preventing glaucoma in the offspring.
Assuntos
Doenças do Cão/diagnóstico , Glaucoma de Ângulo Fechado/veterinária , Gonioscopia/veterinária , Tonometria Ocular/veterinária , Animais , Cruzamento , Córnea/anatomia & histologia , Doenças do Cão/genética , Cães , Feminino , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/diagnóstico , Gonioscopia/normas , Iris/anatomia & histologia , Ligamentos , Masculino , Valor Preditivo dos Testes , Tonometria Ocular/normasRESUMO
OBJECTIVE: A comparative study was performed in order to identify aqueous humor amino acids possibly involved in cataract formation in farmed Atlantic salmon. METHODS: Aqueous humor amino acids from farmed salmons with and without cataract were compared with levels in wild salmon and other animals of different evolutionary levels such as frog, crocodile, turkey, goose, minke whale, and cattle. Serum samples from wild and farmed salmon and minke whale were also analyzed. RESULTS: The total amino acid concentration was lower in aqueous humor obtained from salmon, frog and crocodile compared to birds and mammals. Wild salmon had a higher content of amino acids than farmed salmon. Asparagine was absent in salmon aqueous humor and serum. Aqueous humor proline was readily detectable in wild salmon, birds, whale, and cattle, but not detectable in farmed salmon, frog and crocodile. The aqueous humor concentration of taurine was about seven- and fifty-fold lower compared to serum in wild and farmed salmon, respectively. The corresponding ratio in minke whale was 1:2. CONCLUSIONS: The results indicate a blood- aqueous barrier for taurine in farmed salmon. The lower total amino acid concentration and low aqueous humor proline concentration in farmed salmon should be further investigated.
Assuntos
Aminoácidos/análise , Humor Aquoso/metabolismo , Salmão/metabolismo , Aminoácidos/sangue , Animais , Animais Selvagens , Aquicultura , Catarata/metabolismo , Salmão/sangue , Salmão/classificaçãoRESUMO
ANIMAL STUDIED: A tumor of the left eye with involvement of the brain and kidney was diagnosed in a 4-year-old Neapolitan mastiff. PROCEDURE: The dog presented with acute glaucoma of the left eye. Peripheral corneal vascularization and severe corneal edema obscured examination of deeper structures. Because of concurrent progressive neurologic signs the dog was euthanized and a postmortem examination was performed. The eyes, brain and samples from the lung, heart, liver and kidneys were fixed in 4% neutral buffered formalin and embedded in paraffin wax. Sections were examined by light microscopy including histochemical and immunohistochemical staining. RESULTS: The ocular tumor originated from the ciliary body and was composed of small islets and cords of poorly differentiated, oval to polyhedral cells surrounded by abundant ground substance. Areas with chondroid differentiation were observed. Rosettes were not found. Metastases with the same morphology were present in the brain and in one kidney. CONCLUSION: An intraocular malignant teratoid medulloepithelioma with metastases to the brain and kidney is presented.
Assuntos
Neoplasias Encefálicas/veterinária , Doenças do Cão/patologia , Neoplasias Oculares/veterinária , Neoplasias Renais/veterinária , Tumores Neuroectodérmicos Primitivos/veterinária , Teratoma/veterinária , Animais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Cães , Olho/patologia , Neoplasias Oculares/patologia , Evolução Fatal , Feminino , Imuno-Histoquímica/veterinária , Neoplasias Renais/patologia , Neoplasias Renais/secundário , Tumores Neuroectodérmicos Primitivos/patologia , Tumores Neuroectodérmicos Primitivos/secundário , Teratoma/patologia , Teratoma/secundárioRESUMO
A retrospective histopathologic study of primary glaucoma in the Norwegian Elkhound was undertaken with the study of 9 clinically normal eyes and 22 glaucomatous eyes. All glaucomatous eyes showed goniodysgenesis as manifested by pectinate ligament dysplasia and/or trabecular meshwork dysplasia. Cystic degeneration of the iridociliary epithelial and/or peripheral retina was present in a high percentage of both normotensive and glaucomatous eyes. Utilizing the scheme proposed by Smith et al. (Veterinary and Comparative Ophthalmology 1993; 3: 16-28) the morphology of this disease in the Norwegian Elkhound would be classified as an open-angle, closed-cleft glaucoma, with histopathologic alterations of the outflow pathway similar to that described in other breeds with primary glaucoma.
Assuntos
Doenças do Cão/epidemiologia , Glaucoma de Ângulo Aberto/veterinária , Animais , Estudos de Casos e Controles , Doenças do Cão/etiologia , Cães , Feminino , Glaucoma de Ângulo Aberto/epidemiologia , Masculino , Noruega/epidemiologia , Linhagem , Registros/veterinária , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the absorbance of ultraviolet radiation (UVR) in the aqueous humor of various animal species in relation to the ambient radiation of their respective habitats, and to identify substances responsible for this absorbance. Representatives of all five classes (fish, amphibian, reptile, bird, and mammal) have been tested. METHODS: Absorbance was recorded using a spectrophotometer. The ascorbic and uric acid concentrations were determined by HPLC, and the amino acid profiles with an automatic analyzer. Screening for potential UV-absorbing substances was performed by HPLC and a total of 12 species were examined, 7 of them birds. RESULTS: UV-absorbing substances in the aqueous humor were proteins, tryptophan, tyrosine and ascorbic and uric acid. In addition, an unknown UV-absorbing component present in bird aqueous humor caused a high, red-shifted UV-absorbance spectrum, particularly in tentatively heavily exposed species such as goose when migrating at 10,000 m altitude. By comparison, the UV absorbance above the 288-nm wavelength was low in the aqueous humor of fish, frogs, aquatic mammals and two ground-living birds. The crocodile, whose aqueous humor contained significant amounts of both ascorbic and uric acid, revealed a concentration mechanism for ascorbic acid. CONCLUSIONS: The UV absorbance of aqueous humor varies considerably from one species to the next, and independent of class. It is noteworthy that the species being at highest risk for high-dose UV exposure, the migrating goose, showed the most red-shifted spectrum.