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E Zrenner

Publications and source records attributed to E Zrenner.

At least 127 records · Page 7Linked to original sources
PubMed1997

Retinoschisislike alterations in the mouse eye caused by gene targeting of the Norrie disease gene.

PURPOSE: To investigate the retinal function and morphology of mice carrying a replacement mutation in exon 2 of the Norrie disease gene. METHODS: Recently, Norrie disease mutant mice have been generated using gene targeting technology. The mutation removes the 56 N-terminal amino acids of the Norrie gene product. Ganzfeld electroretinograms (ERGs) were obtained in five animals hemizygous or homozygous for the mutant gene and in three female animals heterozygous for the mutant gene. As controls, three males carrying the wild-type gene were examined. Electroretinogram testing included rod a- and b-wave V-log I functions, oscillatory potentials, and cone responses. The fundus morphology has been visualized by scanning laser ophthalmoscopy. RESULTS: Rod and cone ERG responses and fundus morphology were not significantly different among female heterozygotes and wild-type mice. In contrast, the hemizygous mice displayed a severe loss of ERG b-wave, leading to a negatively shaped scotopic ERG and a marked reduction of oscillatory potentials. The a-wave was normal at low intensities, and only with brighter flashes was there a moderate amplitude loss. Cone amplitudes were barely recordable in the gene-targeted males. Ophthalmoscopy revealed snowflakelike vitreal changes, retinoschisis, and pigment epithelium irregularities in hemizygotes and homozygotes, but no changes in female heterozygotes. CONCLUSIONS: The negatively shaped scotopic ERG in male mice with a Norrie disease gene mutation probably was caused by retinoschisis. Pigment epithelial changes and degenerations of the outer retina are relatively mild. These findings may be a clue to the embryonal retinoschisislike pathogenesis of Norrie disease in humans or it may indicate a different expression of the Norrie disease gene defect in mice compared to that in humans.

Animals↗
PubMed1997

Evaluation of the gene encoding the tissue inhibitor of metalloproteinases-3 in various maculopathies.

PURPOSE: Mutations in the gene encoding the tissue inhibitor of metalloproteinases-3 (TIMP3) have been shown previously to cause Sorsby's fundus dystrophy, an autosomal-dominant disorder characterized by extracellular matrix irregularities in Bruch's membrane. To assess the involvement of TIMP3 in a variety of other macular dystrophies, the authors have screened this gene for disease-causing mutations in age-related macular degeneration (AMD), adult vitelliform macular dystrophy (AVMD), central areolar choroidal dystrophy (CACD), syndrome-associated macular dystrophies, cone-rod dystrophy, and a group with unspecified macular degeneration. METHODS: Single-stranded conformational analysis of the entire coding region was performed using the polymerase chain reaction and oligonucleotide primers flanking the five exons of the TIMP3 gene as well as the putative promotor region and a highly conserved fragment of the 3'-untranslated region. The authors analyzed a total of 217 patients, including 143 patients with AMD, 28 patients with AVMD, 21 patients with CACD, and 25 patients with other forms of macular dystrophy. RESULTS: In the 217 patients analyzed, the authors have identified one sequence alteration (a G-to-C base change) in the 5'-untranslated region in a patient with AMD. However, the functional consequences of this mutation are not clear. No other disease-causing mutations were found. The authors have characterized a frequent intragenic polymorphism in exon 3 of the TIMP3 gene (heterozygosity = 0.57) that will be useful for genetic linkage or allele sharing analyses or both. CONCLUSIONS: The authors' results suggest that TIMP3 is not a major factor in the cause of AMD, AVMD, and CACD. Thus far, Sorsby's fundus dystrophy appears to be the only phenotype known to be associated with mutations in TIMP3.

Aged↗
PubMed1997

Persistent decrease of the dopamine-synthesizing enzyme tyrosine hydroxylase in the rhesus monkey retina after chronic lead exposure.

One of the toxic effects of lead in the CNS is an altered functional state of the catecholamine system, especially a reduction in the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. Here we report on a lead-induced decrease in TH-content in neurones of the rhesus monkey retina. Rhesus monkeys were pre- and postnatally exposed to 0, 350, or 600 ppm of lead acetate (Pb) in the diet over 9 years. Lead exposure was followed by a 35-month period of lead-free diet. During this period, blood lead levels of the treated animals declined to nearly those of the untreated controls. Subsequently the animals were sacrificed and the retinas processed for TH immunocytochemistry. The fluorescent dye FITC was used to visualise the antibody reaction. Photometric measurements of the fluorescence intensity of stained neurones were made with a laser scanning microscope. In the rhesus monkey retina two types of TH-immunoreactive neurones are present. In the bright fluorescent type, lead exposure resulted in decreased fluorescence intensity and altered the intensity profile of the TH-immunoreactive cells in a dose-dependent manner. In these cells, fluorescence intensity was 0.53 and 0.22 for 350 ppm Pb and 600 ppm Pb respectively when the fluorescence intensity of the untreated controls (0 ppm Pb) is taken as 1. Both lead doses also reduced the number of ascending fibres in the inner nuclear layer and the dense staining of fibres in sublayer 1 of the inner plexiform layer. The weakly fluorescent cell type disappeared to a large extent under 350 ppm Pb treatment and was not detectable in the 600 ppm Pb group. The results demonstrate that lead exposure affects the dopaminergic retinal amacrine cells by reducing the TH-content in these neurones and that this neurotoxic effect persists beyond the end of exposure.

Animals↗
PubMed1996

[Noise field screening. Results of a television field study for detection of visual field defects].

White noise field campimetry is able to transform usually negative scotomas immediately into perceivable visual field defects. As this method needs a monitor, the obvious solution was to evaluate the suitability of the noise field stimulus broadcasted to home TV sets. Therefore, in cooperation with the "Süddeutscher Rundfunk" (SDR) as well as several health insurance companies ("AOK Baden-Württemberg" and other "RVO-Kassen"), approximately 300,000 viewers were invited to take this test after receiving brief information and instruction. There were 531 calls for questionnaires to document the subjects' findings and the results of a subsequent ophthalmological examination. In most cases this clarified the perceived noise field defect. Out of 127 evaluable questionnaires, 78 cases did not show any relevant ophthalmological pathology; this held true especially for lesions of the visual pathway. However, in 49 persons the ophthalmologists detected pathological findings; in 20 of these, the scotomas were previously unknown to the physicians. Glaucomatous optic neuropathy and macular degeneration were most frequently diagnosed as causing the white noise field defects. Finally, some preliminary estimates of the costs and benefit of this study are presented.

Adolescent↗
PubMed1996

Bradykinin receptor inhibition affects the rod b-wave in the cat electroretinogram.

In 10 anaesthetized cats, electroretinographic (ERG) measurements were carried out to further elucidate the involvement of bradykinin as a substrate component of the renin-angiotensin system in retinal neurotransmission. Reducing angiotensin II concentration by angiotensin-converting enzyme (ACE) inhibition increased sensitivity (0.5 log units) and gain (50%) of the rod b-wave amplitude. The b-wave implicit time was decreased only at high stimulus intensities (> 10(-2) cd/m). Blocking bradykinin receptors specifically decreased rod b-wave implicit time for all intensities, while its amplitude remained unaffected. Bradykinin effects were independent of alterations of angiotensin II activity. We therefore suggest that bradykinin influences inner retinal signal processing, hereby further supporting the hypothesis of a renin-angiotensin system involvement in retinal neurotransmission.

Angiotensin II↗
PubMed1996

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

Amino Acid Sequence↗
PubMed1996

[Mobilization of intraocular foreign bodies by magnetic resonance tomography].

A 49-year-old patient suffered from a binocular perforating trauma with metal foreign bodies in 1974. During an MRI examination in 1992 for a lumbar spine herniation a metal foreign body was mobilised from the deeper vitreal and retinal area, now causing optical disturbances freely floating in the anterior vitreous. Refusing an operation, the patient, an electrical engineer, tried himself to remove the foreign body out of the optical axis by exposing his head to the electro-magnetic field of an induction coil (pulsed magnetic induction B at t0 of 0.26 Tesla). The foreign body was split into multiple small parts no longer disturbing the patient. To early detect a siderosis regular ophthalmological controls including ERG are necessary. This example stresses that even small intraocular metal foreign bodies are a contraindication for the usually applied field strength of MRI examinations.

Electromagnetic Fields↗
PubMed1996

[Visual image in high ametropia. Computer-assisted simulation with optic ray calculation].

PURPOSE: A computer program developed by the authors allows to calculate the path of light rays coming from an object through all the refractive surfaces of a Gullstrand model eye until it reaches the retina. METHOD: The program calculates several hundred light rays for every point of a given object. A menue allows to modify optical and morphological parameters in an interactive way. For instance, the indices of refraction, the radii of the cornea and of the cristalline lens, as well as the length of the bulbus can be modified. Further, one can add seeing aids such as eye glasses or a contact lens, or implant an artificial intraocular lens. The seeing aids may be decentered and/or tilted. RESULTS: The code calculates also the visual impression by projecting the image from the retina back to a screen at the distance of the object, where the human brain "sees" the object. For image interpretation we use a normal Gullstrand eye with a very small aperture stop. In this way we can simulate the visual mapping (visual impression) of a corrected or uncorrected ametropia. CONCLUSIONS: In this paper we present two nontrivial examples: we calculate the regional polyopia ("Bildverdoppelung") and the annular scotoma which appear whenever a high myopia or aphakia are corrected by eye glasses.

Computer Simulation↗
PubMed1996

Analysis of 21 Stargardt's disease families confirms a major locus on chromosome 1p with evidence for non-allelic heterogeneity in a minority of cases.

BACKGROUND: Autosomal recessive Stargardt's disease is a macular degeneration characterised by a juvenile onset and a rapidly progressive course resulting in an atrophic macular area typically surrounded by yellowish retinal flecks. METHOD: The disease locus has previously been assigned to markers from chromosome 1p21-p13 by genetic linkage analysis in eight multiplex Stargardt's disease families. RESULTS: In an extended analysis, the assignment to chromosome 1p was confirmed in the majority of the 21 families with Stargardt's disease who were studied. In addition, a series of recombinant chromosomes further narrowed the Stargardt's disease region to an approximately 3 cM interval between markers at D1S424 and D1S497. CONCLUSION: Multipoint linkage analysis most probably excludes this locus in three of these families suggesting non-allelic heterogeneity with at least one additional minor Stargardt's disease locus.

Chromosomes, Human, Pair 1↗
PubMed1996

ERG campimetry using a multi-input stimulation technique for mapping of retinal function in the central visual field.

The m-sequence stimulation technique that has previously been described allows simultaneous recording of many local electroretinograms (ERGs). For topographical mapping of cone function in the central retina ERG traces from 61 retinal areas were recorded during a 4-min period in 20 normal volunteers and 4 patients with age-related macular degeneration, Stargardt's disease, choroidal atrophy, and polymyalgia associated with visual field loss. The local photopic luminance response was analyzed in each of the 61 areas. In the 2 patients with macular disease central defects were detected, in the remaining patients local defects were found outside the macular region. The method of multifocal ERG recordings provides the possibility of objective testing of visual fields when the outer retinal layers are affected.

Adult↗
PubMed1996

Leber's hereditary optic neuropathy: clinical and molecular genetic results obtained in a family with a new point mutation at nucleotide position 14498 in the ND 6 gene.

Mitochondrial DNA mutations at nucleotide position (np) 3460 in the ND 1 gene, np 11778 in the ND 4 gene, and np 14484 in the ND 6 gene are commonly considered to be associated with the clinical features of Leber's hereditary optic neuropathy (LHON) and account for the majority of LHON cases. Recently, a further mutation in the mtDNA at np 14459 was detected. Herein we report the clinical and the most relevant molecular genetic findings obtained in a LHON family with a new mitochondrial DNA mutations at np 14498 in the ND 6 gene. Clinical and historical data were collected over four generations on three affected and five yet unaffected relatives of the maternal line in this family. All three patients and four of their relatives underwent molecular genetic examination. Two patients and five relatives were also studied clinically. All patients exhibited typical clinical features of LHON. In all yet unaffected relatives, various degrees of peripapillary microangiopathy were found. Molecular analysis did not reveal any of the common LHON mutations. Sequence analysis of the mtDNA of one patient was performed and showed a thymine-to-cytosine exchange at np 14498 in the ND 6 gene, leading to the replacement of an evolutionary highly conserved tyrosine by a cysteine residue. The mutation was not found among 70 other LHON lineages and 180 controls. The new mutation at np 14498 lies in the vicinity of the LHON-related mutations at np 14484 and of the recently described mutation at np 14459, in a region constituting the most evolutionarily conserved part of this polypeptide. That the new mutation at np 14498 is found within this highly conserved region and was not present in any controls implies that this mutation is responsible for LHON in this family.

Adolescent↗
PubMed1996

Factors that influence the increase in the electroretinogram 30-Hz flicker amplitude during light adaptation.

Cone responses of the electroretinogramm (ERG) surprisingly increase during the first few minutes of light adaptation. In this study, especially the influence of rods and cones on this not yet understood phenomenon was examined. In 100 subjects a dark-adapted ERG was recorded. Afterward, two 30-Hz flicker recordings were performed, the first one after 1 min and the second one after 10 min of light adaptation. The relative flicker-amplitude increase was calculated. The influence of the ERG standard rod response and the 30-Hz flicker amplitude itself on the 30-Hz flicker-amplitude increase was estimated. The mean increase in the 30-Hz flicker amplitude was 51.7%. There was no significant correlation between the standard rod amplitude and the amplitude growth (r = 0.031). The correlation between the 30-Hz flicker amplitude itself and the increase in cone response was -0.426 (P < or = 0.001). The lower the cone flicker amplitude was after 1 min of light adaptation, the bigger was the amplitude increase. This might either be due to saturation or indicate that the flicker-amplitude increase is mainly related to cone function rather than being dependent on the rod-response amplitude.

Adaptation, Ocular↗
PubMed1996

Electroretinographic campimetry in a patient with crystalline retinopathy.

We report the findings we obtained by multifocal electroretinography (ERG) in a patient with crystalline retinopathy. Although the conventional Ganzfeld (full-field) ERG was within the normal range, the amplitudes were reduced and implicit times were delayed in the parafoveolar region in the multifocal ERG. To our knowledge, this is the first report on crystalline retinopathy investigated with this spatially differentiating electrophysiologic method, which is useful for the detection of early change in this disease.

Adult↗
PubMed1995

Studies on the role of the retinal dopamine/melatonin system in experimental refractive errors in chickens.

We have found that development of both deprivation-induced and lens-induced refractive errors in chickens implicates changes of the diurnal growth rhythms in the eye (Fig. 1). Because the major diurnal oscillator in the eye is expressed by the retinal dopamine/melatonin system, effects of drugs were studied that change retinal dopamine and/or serotonin levels. Vehicle-injected and drug-injected eyes treated with either translucent occluders or lenses were compared to focus on visual growth mechanisms. Retinal biogenic amine levels were measured at the end of each experiment by HPLC with electrochemical detection. For reserpine (which was most extensively studied) electroretinograms were recorded to test retinal function [Fig. 3 (C)] and catecholaminergic and serotonergic retinal neurons were observed by immunohistochemical labelling [Fig. 3(D)]. Deprivation myopia was readily altered by a single intravitreal injection of drugs that affected retinal dopamine or serotonin levels; reserpine which depleted both serotonin and dopamine stores blocked deprivation myopia very efficiently [Fig. 3(A)], whereas 5,7-dihydroxy-tryptamine (5,7-DHT), sulpiride, melatonin and Sch23390 could enhance deprivation myopia (Table 1, Fig. 5). In contrast to other procedures that were previously employed to block deprivation myopia (6-OHDA injections or continuous light) and which had no significant effect on lens-induced refractive errors, reserpine also affected lens-induced changes in eye growth. At lower doses, the effect was selective for negative lenses (Fig. 4). We found that the individual retinal dopamine levels were very variable among individuals but were correlated in both eyes of an animal; a similar variability was previously found with regard to deprivation myopia. To test a hypothesis raised by Li, Schaeffel, Kohler and Zrenner [(1992) Visual Neuroscience, 9, 483-492] that individual dopamine levels might determine the susceptibility to deprivation myopia, refractive errors were correlated with dopamine levels in occluded and untreated eyes of monocularly deprived chickens (Fig. 6). The hypothesis was rejected. Although it has been previously found that the static retinal tissue levels of dopamine are not altered by lens treatment, subtle changes in the ratio of DOPAC to dopamine were detected in the present study. The result indicates that retinal dopamine might be implicated also in lens-induced growth changes. Surprisingly, the changes were in the opposite direction for deprivation and negative lenses although both produce myopia. Currently, there is evidence that deprivation-induced and lens-induced refractive errors in chicks are produced by different mechanisms. However, findings (1), (3) and (5) suggest that there may also be common features. Although it has not yet been resolved how both mechanisms merge to produce the appropriate axial eye growth rates, we propose a scheme (Fig. 7).

5,7-Dihydroxytryptamine↗
PubMed1995

Extensive intrafamilial and interfamilial phenotypic variation among patients with autosomal dominant retinal dystrophy and mutations in the human RDS/peripherin gene.

Clinical phenotypes of patients with mutations in the human RDS/peripherin gene are described. A 67-year-old woman, who carried a 1 base pair deletion in codon 307, presented with typical late onset autosomal dominant retinitis pigmentosa (RP). In another autosomal dominant pedigree, a nonsense mutation at codon 46 caused 'inverse' retinitis pigmentosa-like fundus changes associated with progressive cone-rod degeneration in a 58-year-old man, whereas his 40-year-old son presented with yellow deposits in the retinal pigment epithelial layer resembling a pattern dystrophy, and with moderately reduced rod and cone function, as determined by two colour dark adapted threshold perimetry and electroretinography. It is suggested that both clinical pictures within this latter family may represent manifestations of fundus flavimaculatus. The clinical data of the three patients provide further evidence for the remarkable variety of disease expression within and between families with mutations in the RDS/peripherin gene. Currently, the most comprehensive statement could be that RDS/peripherin mutations are associated either with typical RP or with various forms of flecked retinal disease.

Adult↗
PubMed1995

Selective cone dystrophy with protan genotype.

PURPOSE: To determine the functional defects in two male patients with progressive cone dystrophy and hybrid L-M cone pigment genes. METHODS: Clinical evaluation, standard electroretinography, and electrooculography were performed in two affected patients and two family members. Measurements of spectral sensitivity and transient tritanopia were made in both patients. RESULTS: In the patients, visual acuity varied between 20/50 and 20/100. The electroretinogram showed reduced flicker responses. When light adapted, a-wave amplitudes were borderline, but b-wave amplitudes were reduced severely. Electroretinography with chromatic stimuli showed a difference between well-preserved responses to green and markedly reduced responses to red stimuli. Spectral sensitivity measurement revealed a lack of L (long-wavelength sensitive; red) cone function and normal function of the S (short-wavelength sensitive; blue) and M (middle-wavelength sensitive; green) cones. Transient tritanopia was abnormal, indicating a severe disturbance of cone-cone interaction. CONCLUSIONS: Progressive cone dystrophy with predominant dysfunction of L cones exists in both patients. The cone dystrophy may be caused by a rearrangement of the X-chromosome pigment gene array that is associated with the deletion of L-cone sequences and the formation of hybrid L-M cone pigment genes. It cannot be excluded, however, that both patients have protanopia and that cone dystrophy developed because of other causes.

Adult↗