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Kristina Narfström

Publications and source records attributed to Kristina Narfström.

16 recordsLinked to original sources
PubMed2006

Electroretinographic findings in the Standard Wire Haired Dachshund with inherited early onset cone-rod dystrophy.

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.

Animals↗
PubMed2006

Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dogs.

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

Animals↗
PubMed2006

A(max) is the best a-wave measure for classifying Abyssinian cat rod/cone dystrophy.

AIM: To see if any a-wave measure segregated normal cats from those affected by a recessively inherited Abyssinian rod/cone dystrophy more efficiently than a(max) to scotopic I(max). METHOD: A-waves to electroretinograms (ERGs) evoked by a 4 cd x s/m(2) scotopic flash were extracted from 241 ERG sessions using 108 cats. They were either wild type or from an affected Abyssinian stock. Fourty four were bred by back-crossing to have a 50% probability of being affected. Most were diagnosed by retinal appearance or by the pattern of loss in a long protocol ERG. Eight were still unclassified. The diagnostic efficiency of amplitudes at 7, 8, 9, and 10 ms and a(max), of a(max) peak time, age at testing, and the main components of principal components factor analysis were compared by scaling their ability to segregate affected and normal cats. RESULTS: Variance and overlap between the groups both decreased as time along the a-wave increased. The loading of each animal on the largest factor also gave considerable overlap. There was a small absolute separation between groups when a(max) itself was used. Age and peak time were uncorrelated with disease. The light intensity used could be calculated to be equivalent to one sufficient for about 75% of full saturation in man. CONCLUSION: A(max) is a simple measure that is already in routine clinical use. When the flash is very bright and the animal fully dark adapted, this single measure is the most efficient sign of this rod/cone degeneration and possibly of all degenerations involving rods.

Animals↗
PubMed2006

The electroretinogram components in Abyssinian cats with hereditary retinal degeneration.

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.

Animals↗
PubMed2006

Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration.

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.

Animals↗
PubMed2005

In vivo confocal imaging of the retina in animal models using scanning laser ophthalmoscopy.

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

Animals↗
PubMed2005

Morphological changes in the anterior segment of the Abyssinian cat eye with hereditary rod-cone 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.

Animals↗
PubMed2005

Assessment of retinal function and characterization of lysosomal storage body accumulation in the retinas and brains of Tibetan Terriers with ceroid-lipofuscinosis.

OBJECTIVE: To characterize lysosomal storage body accumulation in the retina and brain of Tibetan Terriers with ceroid-lipofuscinosis and determine whether the disease in these dogs is accompanied by impaired retinal function and retinal degeneration. ANIMALS: Three 7- to 10-year-old Tibetan Terriers with ceroid-lipofuscinosis and 1 healthy 5-year-old Tibetan Terrier. PROCEDURE: Owners completed a questionnaire to identify behavioral and physical signs indicative of ceroid-lipofuscinosis. Neurologic, behavioral, and ophthalmologic evaluations, including full-field electroretinograms, were performed on each dog. Fluorescence, light, and electron microscopy were performed on specimens of retina, cerebral cortex, and cerebellum of all dogs postmortem. RESULTS: Behavioral assessments of the affected dogs revealed moderate visual impairment in low-light conditions but good vision in bright light. On funduscopic evaluation of these dogs, abnormalities detected ranged from none to signs of moderately advanced retinal degeneration. Compared with findings in the control dog, electroretinography revealed depressed rod cell function with some impairment of cone cell function in the affected dogs. Morphologically, disease-specific storage bodies were detected in retinal Müller cells and neurons, particularly in ganglion cells, and in cells of the cerebral cortex and cerebellum in affected dogs. Substantial photoreceptor cell loss and disruption of photoreceptor outer segment morphology appeared to develop late in the disease. IMPLICATIONS FOR HUMAN MEDICINE: The similarities between ceroid-lipofuscinosis in Tibetan Terriers and some forms of ceroid-lipofuscinosis in humans suggest that the canine disease may have a genetic and biochemical basis similar to that of one of the ceroid-lipofuscinosis disorders in humans.

Adaptation, Ocular↗
PubMed2004

Optimal discrimination of an Abyssinian cat recessive retinal degeneration: a short electroretinogram protocol is more efficient than a long one.

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.

Animals↗
PubMed2003

Gene transfer in the RPE65 null mutation dog: relationship between construct volume, visual behavior and electroretinographic (ERG) results.

In vivo gene transfer in a large group of RPE65 null mutation dogs have been recently performed. The present study was aimed at determining, through visual behavioral and electroretinographic (ERG) testing, if there is a volume effect of the gene construct administered. Eleven Beagle-Briard dogs homozygous for the RPE65 null mutation and two unaffected control dogs were included. Affected animals were unilaterally treated with either a high (70-100 micro1; N = 6) or a low volume (30-60 microl; N = 5) of subretinally injected rAAV.RPE65 construct, at the age of 4 months to 2.5 years. Fellow eyes were treated with a subretinal injection of rAAV.GFP or sham operated and used as internal controls. Retinal function was measured pre- and 10-12 weeks post-surgically, using simultaneous bilateral full-field flash ERGs. A significant improvement in all ERG responses studied was identified for the high volume treated group compared to pre-surgical parameters. A significant improvement for the high intensity scotopic a-wave response for the low volume rAAV.RPE65 treated group was also found. Objective and subjective dim and day light visual maze testing, in eight of the affected treated animals, and the two control dogs, revealed better vision in daylight than in dim light for all animals. Vision in dogs treated with the high volume of gene construct was significantly better in day light than in dim light. No significant difference was noted between day and dim light testing for the control group or those animals treated with a low volume of the gene construct. Significantly better vision was noted in the control group when compared with the low volume group under dim light conditions, and the high volume group under day light conditions. No significant difference in functional vision could be identified between the high volume treated animals and control animals in day light conditions. These findings support the hypothesis that functional vision is improved by subretinal rAAV.RPE65 injection in a volume-dependent manner.

Animals↗
PubMed2003

Lens sparing pars plana vitrectomy and retinal transplantation in cats.

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.

Animals↗
PubMed2003

Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog.

PURPOSE: To assess the efficacy of AAV-mediated gene therapy to restore vision in a large number of RPE65(-/-) dogs and to determine whether systemic and local side effects are caused by the treatment. METHODS: Normal RPE65 dog cDNA was subcloned into an rAAV vector under control of a cytomegalovirus promoter, and an AAV.GFP control vector was also produced with the titers 2 x 10(12) particles/mL and 2 x 10(10) transducing U/mL, respectively. RPE65(-/-) dogs, aged 4 to 30 months were treated with subretinal injections of the AAV.RPE65 and control vectors, respectively, in each eye, and three 24- to 30-month-old normal control dogs with the latter. Baseline and postoperative systemic and ophthalmic examinations, blood screenings, vision testing, and electroretinography (ERG) were performed. Two RPE65(-/-) dogs were killed at 3 and 6 months after treatment for morphologic examination of the retinas. RESULTS: RPE65(-/-) dogs were practically blind from birth with nonrecordable or low-amplitude ERGs. Construct injections or sham surgeries were performed in 28 eyes; 11 were injected subretinally with the AAV.RPE65 construct. ERGs at 3 months after surgery showed that in the latter eyes, dark-adapted b-wave amplitudes recovered to an average of 28% of normal, and light adapted b-wave amplitudes to 32% of normal. ERG amplitudes were not reduced during a 6- to 9-month follow-up. No systemic side effects were observed, but uveitis developed in nine AAV.RPE65-treated eyes. No uveitis was observed in the eyes treated with the control vector. Immunocytochemistry showed expression of RPE65 in the retinal pigment epithelium (RPE) of AAV.RPE65-treated eyes. Fluorescence microscopy showed expression of green fluorescent protein (GFP) in the RPE and, to a lesser extent, in the neural retinas of AAV.GFP-treated eyes. Ultrastructurally, a reversal of RPE lipid droplet accumulation was observed at the AAV.RPE65 transgene injection site, but not at the site of injection of the control vector. CONCLUSIONS: In 10 of 11 treated RPE65(-/-) eyes, gene transfer resulted in development of vision, both subjectively apparent by loss of nystagmus, and objectively recorded by ERG. Structurally, there was reversal of lipid droplet accumulation in the RPE. Uveitis developed in 75% of the transgene-treated eyes, a complication possibly due to an immunopathogenic response to the RPE65 molecule.

Animals↗
PubMed2002

Guidelines for clinical electroretinography in the dog.

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.

Animals↗
PubMedDate not supplied

Abnormal dark-adapted ERG in cats heterozygous for a recessively inherited rod-cone degeneration.

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.

Animals↗
PubMedDate not supplied

Cerebral ventricular size in developing normal kittens measured by ultrasonography.

To evaluate the age of fontanelle closure of normal kittens and the size of their lateral ventricles, 50 ultrasonographic examinations using the bregmatic fontanelle as an acoustic window were made. Seven kittens, laboratory animals, were included in the study. To verify the location of the lateral ventricle, two of the kittens were sacrificed as neonates. In one of them ink was injected prior to autopsy into one lateral ventricle under sonographic guidance. In a longitudinal study of five of the kittens, the skull depth and the depth of the central part of the lateral ventricle reproduced in a longitudinal view could be measured up to the age of about 5 months. During that period, the skull depth increased from a median value of 1.95 cm (1.92-1.98) in a seven-day-old cat to 2.58 cm (2.52-2.59) in a 154-day-old cat, while the afore-mentioned ventricle values increased from 0.3 mm to 1.1 mm.

Animals↗