Eberhart Zrenner

University of Tuebingen, Tübingen, Baden-Württemberg, Germany

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Publications (474)1367.18 Total impact

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    ABSTRACT: Retinitis Pigmentosa involves a hereditary degeneration of photoreceptors by as yet unresolved mechanisms. The secretable protein α-Klotho has a function related to ageing processes, and α-Klotho deficient mice have reduced lifespan and declining functions in several tissues. Here, we studied Klotho in connection with inherited photoreceptor degeneration. Increased nuclear immunostaining for α-Klotho protein was seen in degenerating photoreceptors in four different Retinitis Pigmentosa models (rd1, rd2 mice; P23H, S334ter rhodopsin mutant rats). Correspondingly, in rd1 retina α-Klotho mRNA expression was significantly upregulated. Moreover, immunostaining for another Klotho family protein, β-Klotho, also co-localised with degenerating rd1 photoreceptors. The rd1 retina displayed reduced levels of fibroblast growth factor (FGF) 15, a member of the FGF subfamily for which Klotho acts as a co-receptor. Exogenous α-Klotho protein added to retinal explant cultures did not affect cell death in rd1 retinae, but caused a severe layer disordering in wild-type retinae. Our work suggests Klotho as a novel player in the retina, with a clear connection to photoreceptor cell death as well as with an influence on retinal organization. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 06/2013; · 4.24 Impact Factor
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    ABSTRACT: PURPOSE: This study aimed to quantify the impact of exposure to high altitude on individual layers of the cornea in regard to central corneal thickness and the geometry of the anterior chamber angle. This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. METHODS: Anterior segment spectral domain optical coherence tomography was used to quantify changes in individual corneal layers and to study anterior chamber angle (ACA) and angle opening distance (AOD). Peripheral oxygen saturation, heart rate, and scores of acute mountain sickness (AMS) were assessed in 14 healthy subjects at baseline (341m) and altitude (4559m) for respective correlations. RESULTS: Longitudinal analysis revealed a significant (p<0.05) increase of central corneal thickness (CCT) during altitude exposure (CCTbaseline = 539.27±32.30μm; CCTday1 = 558.87±29.39μm; CCTday3 = 567.17±33.40μm; mean±sd) due to stromal oedema. This change was completely reversible upon descent. Geometric measures of aqueous outflow structures remained consistent with no significant changes in AOD or ACA. Incidence of AMS on day1 was 64% followed by a decrease in AMS scores over time spent at high altitude; while AMS correlated significantly with stromal oedema formation just after arrival (r=0.71; p=0.01), no correlation was found on day3 (r=0.05; p=0.87); no correlations were found for vital parameters. CONCLUSIONS: Significant stromal oedema was found during exposure to high altitude in healthy subjects. This seems to occur due to decreased atmospheric pressure under hypoxia but independent of systemic acclimatization. Other measures of anterior chamber geometry remained stable during the challenge to hypoxic conditions at high altitude.
    Investigative ophthalmology & visual science 06/2013; · 3.43 Impact Factor
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    ABSTRACT: Introduction The purpose of this study was to investigate the safety and efficacy of transcorneal electrical stimulation (TES) in patients suffering from retinal artery occlusion (RAO). Methods Twelve patients with central and one patient with branch RAO (age 25–84 years, median 74 years) were enrolled in this prospective, randomized, sham-controlled study. RAO was diagnosed 10 days to 17 months prior to study participation. Patients were treated with TES (5 ms positive followed by 5 ms negative biphasic pulses at 20 Hz; applied with DTL electrodes) for 30 min once a week for 6 consecutive weeks. Patients were randomly assigned to TES with 0 mA (sham, n = 3), 66% (n = 5) or 150% (n = 5) of the patient’s individual electrical phosphene threshold (EPT) at 20 Hz. Best corrected visual acuity, ophthalmology examination and EPT (at 3, 6, 9, 20, 40, 60, and 80 Hz) were determined at baseline and at eight follow-up visits over 17 weeks. During four visits (week 1, 5, 9, and 17) kinetic and static visual fields as well as full-field and multifocal electroretinography were measured. The method of restricted maximum likelihood (P < 0.05, Tukey–Kramer) was used to estimate the development of parameters under treatment. Results TES was tolerated well; no ocular or systemic adverse events were observed except for foreign-body sensation after TES (n = 3). During the study period the slopes of the scotopic a-wave increased significantly (high-intensity flash white 10 cd.s/m2; P = 0.03) in the 150% treatment group. All other parameters in all other groups remained statistically unchanged. Conclusions Although TES was tolerated well, statistically significant improvements were found only for specific a-wave slopes. This is in contradiction to previous smaller, uncontrolled reports. Further studies with larger sample sizes and longer duration might, however, show additional significant effects.
    Ophthalmology and Therapy. 06/2013; 2(1).
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    ABSTRACT: While hypoxia plays a key role in the pathophysiology of many common and well-studied retinal diseases, little is known about the effects of high altitude hypoxia on retinal function. The aim of the current study was to assess retinal function during exposure to high altitude hypoxia using electroretinography (ERG). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Electroretinography was performed in 14 subjects in Tübingen, Germany (341 m) and at high altitude at La Capanna Regina Margherita, Italy (4.559 m) using an extended protocol to assess functional integrity of various retinal layers. To place findings in the context of acute mountain sickness, correlations between ERG measurements and oxygen saturation, heart rate and scores of acute mountain sickness (AMS-C) were calculated. At high altitude the maximum response of the scotopic sensitivity function, the implicit times of the a- and b-wave of the combined rod-cone responses and implicit times of the photopic negative responses (PhNR) were significantly altered. a-wave slopes and i-waves were significantly decreased at high altitude. - The strongest correlation was found for PhNR and SpO2 (r=0.68;p<0.05). Of all tested correlations only the photopic b-wave implicit time (10 cd.s/m&sup2;) was significantly correlated with severity of AMS (r=0.57;p<0.05). ERG data show that retinal function of inner, outer and ganglion cell layer is altered at high altitude hypoxia. Interestingly, the most affected ERG parameters are related to combined rod-cone responses, which indicate that phototransduction and visual processing, especially under conditions of rod-cone interaction, are primarily affected at high altitude.
    Journal of Applied Physiology 05/2013; · 3.43 Impact Factor
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    ABSTRACT: Hereditary retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different forms of RD can be caused by mutations in >100 genes, including >1600 exons. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. So far, NGS is not routinely used in gene diagnostics. We developed a diagnostic NGS pipeline to identify mutations in 170 genetically and clinically unselected RD patients. NGS was applied to 105 RD-associated genes. Underrepresented regions were examined by Sanger sequencing. The NGS approach was successfully established using cases with known sequence alterations. Depending on the initial clinical diagnosis, we identified likely causative mutations in 55% of retinitis pigmentosa and 80% of Bardet-Biedl or Usher syndrome cases. Seventy-one novel mutations in 40 genes were newly associated with RD. The genes USH2A, EYS, ABCA4, and RHO were more frequently affected than others. Occasionally, cases carried mutations in more than one RD-associated gene. In addition, we found possible dominant de-novo mutations in cases with sporadic RD, which implies consequences for counseling of patients and families. NGS-based mutation analyses are reliable and cost-efficient approaches in gene diagnostics of genetically heterogeneous diseases like RD.European Journal of Human Genetics advance online publication, 17 April 2013; doi:10.1038/ejhg.2013.72.
    European journal of human genetics: EJHG 04/2013; · 3.56 Impact Factor
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    ABSTRACT: Purpose: To investigate the presence and distribution of l-kynurenine aminotransferases immunoreactivity in human and animal lenses during cataract formation. Methods: Immunohistochemistry was conducted using polyclonal antibodies against KAT I, KAT II and KAT III on sections of 26 anterior capsules from patients undergoing surgical treatment of anterior subcapsular cataract (ASC) and 22 cataractous lenses from human eyes enucleated because of choroidal malignant melanoma. Additionally, the eyes of 11-month-old DBA/2J mice (6 eyes) were investigated (with KAT I and II). Ten clear human lenses and four BL6 mice lenses were used as controls. Spatial immunoreactivity patterns of enzymes were compared with Periodic Acid - Schiff (PAS)-stained sections. Results: Immunohistochemical analysis revealed presence of KAT I, KAT II and KAT III in extracellular structures of all studied types of cataract in human eyes showing specific pattern of the stain. In cortical cataract, immunoreactivity was observed on cortical lens fibres. In nuclear cataract, KAT II revealed stronger and diffused staining than KAT I. Additionally, both KAT showed more pronounced staining at the edge of small clefts. In normal human lenses, KAT I, II and III, immunoreactivity was not observed. Presence of KAT I and KAT II in the intercellular substance of DBA/2J mice cataract was observed. In BL6 mice lenses without cataract, only weak KAT I and KAT II staining was observed. Conclusions: Presence of l-kynurenine aminotransferases in extracellular matrix (ECM) during human cataract formation suggests that products of l-kynurenine pathway might be involved in mechanisms of cataractogenesis.
    Acta ophthalmologica 04/2013; · 2.44 Impact Factor
  • Wilderness and Environmental Medicine 03/2013; 24(1):82–83. · 0.79 Impact Factor
  • Wilderness and Environmental Medicine 03/2013; 24(1):83. · 0.79 Impact Factor
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    ABSTRACT: This study aims at substituting the essential functions of photoreceptors in patients who are blind owing to untreatable forms of hereditary retinal degenerations. A microelectronic neuroprosthetic device, powered via transdermal inductive transmission, carrying 1500 independent microphotodiode-amplifier-electrode elements on a 9 mm(2) chip, was subretinally implanted in nine blind patients. Light perception (8/9), light localization (7/9), motion detection (5/9, angular speed up to 35 deg s(-1)), grating acuity measurement (6/9, up to 3.3 cycles per degree) and visual acuity measurement with Landolt C-rings (2/9) up to Snellen visual acuity of 20/546 (corresponding to decimal 0.037° or corresponding to 1.43 logMAR (minimum angle of resolution)) were restored via the subretinal implant. Additionally, the identification, localization and discrimination of objects improved significantly (n = 8; p < 0.05 for each subtest) in repeated tests over a nine-month period. Three subjects were able to read letters spontaneously and one subject was able to read letters after training in an alternative-force choice test. Five subjects reported implant-mediated visual perceptions in daily life within a field of 15° of visual angle. Control tests were performed each time with the implant's power source switched off. These data show that subretinal implants can restore visual functions that are useful for daily life.
    Proceedings of the Royal Society B: Biological Sciences 02/2013; 280(1757):20130077. · 5.29 Impact Factor
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    ABSTRACT: Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD.For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9±6.62, female 8, male 4) and 11 patients without AMD (age 66.6±16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards.PATIENTS WITH AMD HAD SIGNIFICANTLY HIGHER AQUEOUS HUMOR LEVELS OF CADMIUM (MEDIAN: 0.70 µmol/L, IQR: 0.40-0.84 vs. 0.06 µmol/L; IQR: 0.01-.018; p = 0.002), cobalt (median: 3.1 µmol/L, IQR: 2.62-3.15 vs. 1.17 µmol/L; IQR: 0.95-1.27; p<0.001), iron (median: 311 µmol/L, IQR: 289-329 vs. 129 µmol/L; IQR: 111-145; p<0.001) and zinc (median: 23.1 µmol/L, IQR: 12.9-32.6 vs. 5.1 µmol/L; IQR: 4.4-9.4; p = 0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 µmol/L, IQR: 11.4-31.3 vs. 49.9 µmol/L; IQR: 32.0-.142.0; p = 0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD.Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD.
    PLoS ONE 02/2013; 8(2):e56734. · 3.53 Impact Factor
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    ABSTRACT: Abstract Purpose: One approach for restoring vision in end-stage hereditary retinal diseases is implantation of a subretinal microphotodiode array. We analyzed retinal fluorescein angiography findings of the implant area. Methods: In this pilot study, patients (n = 11; 10 men, one woman; ages 45.2 ± 8.7 years), with visual acuity of light perception or worse resulting from a hereditary retinal degenerative disease, received active electronic subretinal visual implants. Implants were removed after 4 weeks (n = 7 subjects) or 4 months (n = 4 subjects). Following implantation, regular fluorescein angiography was performed. Regions of retinal capillary loss, microaneurysms, capillary alterations, neovascularization and leakage over the implant were scored at time points T1 (days 1-14), T2 (days 15-28) and T3 (months 3-4). Occurrence and changes of fluorescein angiographic phenomena are reported. Results: In terms of the number of patients in whom retinal alterations were observed (compared to available images) the occurences of the angiographic phenomena (for time points T1, T2 and T3, respectively) were as follows: regions of capillary loss (five of seven, 10 of 11 and five of five patients), microaneurysms (0 of seven, two of 11 and three of five patients), calibre alterations of the capillaries (three of seven, eight of 11 and five of five patients), retinal neovascularization (one of seven, one of 11 and 0 of five) and leakage (three of seven, seven of 11 and four of five). The Friedman test revealed no significant changes in capillary loss, calibre alteration of the capillaries, neovascularization or leakage. Microaneurysms increased significantly (p = 0.037). Conclusions: Subretinal visual implants lead to increased capillary microaneurysms, a possible compensatory mechanism following recovery of inner retinal activity. There were no significant changes in capillary loss, calibre alteration of the capillaries, retinal neovascularization and leakage at 4 months. Further study will determine whether and to what degree long-term vascular changes are affected by the surgical procedure, the implant itself and/or recovery of retinal neuronal activity.
    Current eye research 02/2013; · 1.51 Impact Factor
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    ABSTRACT: Stargardt's disease is an autosomal recessive inherited juvenile macular degeneration and at present no acknowledged science-based therapy is available for these patients. Recently, reports have been published on the effectiveness of electrical stimulation in experimental animal models and in patients with neurodegenerative ocular disease, particularly retinitis pigmentosa. This study included 12 patients with Stargardt's disease who were randomized into one of three groups (n = 4) with 0% (sham), 66% or 150% of the individual electrically stimulated phosphene threshold. Outcome measures of the study were safety and efficacy of transcorneal electrical stimulation (TES) with DTL electrodes in subjective and objective parameters of visual function under therapy. In general TES was well tolerated and no adverse or serious events were noted. Neither Ganzfeld, multifocal ERG, OCT nor visual field testing showed statistically significant changes in any group.
    Der Ophthalmologe 01/2013; 110(1):68-74. · 0.72 Impact Factor
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    ABSTRACT: Morbus Stargardt ist eine autosomal-rezessiv vererbte juvenile Makuladegeneration, für die bis heute keine anerkannte, wissenschaftlich fundierte Therapie existiert. Neuere Berichte über die Wirksamkeit elektrischer Stimulation bei Versuchstieren und Patienten mit neurodegenerativen Augenerkrankungen, v. a. Retinitis pigmentosa, veranlassten uns zur Durchführung einer ersten wissenschaftlichen Untersuchung der therapeutischen Möglichkeiten der Elektrostimulation bei Morbus Stargardt. Die Zielparameter unserer Studie waren die Sicherheit und Wirksamkeit der transkornealen Elektrostimulation (TES) durch Bestimmung subjektiver und objektiver Parameter der Sehfunktion. Hierzu wurden 12 Patienten in 3 Gruppen (n = 4) randomisiert und mit 0% (Sham), 66%, oder 150% ihrer individuellen Schwelle für elektrisch ausgelöste Phosphene über 6 Wochen 1-mal wöchentlich stimuliert. Es traten bei der TES keine unerwünschten Ereignisse oder schwerwiegende unerwünschte Ereignisse auf. Weder im Ganzfeld- oder multifokalen ERG noch im OCT oder der Gesichtsfelduntersuchung konnten statistisch signifikante Änderungen festgestellt werden. Die bestkorrigierte Sehschärfe zeigte eine Verbesserungstendenz in der überschwellig stimulierten Patientengruppe.
    Der Ophthalmologe 01/2013; 110(1). · 0.72 Impact Factor
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    ABSTRACT: BACKGROUND: Participation in first human applications of retinal neuroprosthesis may create psychological stress for blind retinitis pigmentosa patients. The aim of this study was to assess the emotional wellbeing of patients undergoing implantation of a subretinal implant. METHODS: Nine blind patients participating in a pilot trial with subretinal implants were enlisted. The Brief Symptom Inventory (BSI), a short self-report scale of nine primary symptoms, was used to assess reaction to the psychological distress related to study participation. The number and the intensity of symptoms were analysed, and global scores for overall psychological distress (tGSI), severity of reported symptoms (tPDSI), and level number of self-reported symptoms (tPST) were calculated. The questionnaire was administered before implantation, 2-3 times during the trial and before explantation. RESULTS: There were no significant alterations during the trial for the average scores of the nine primary symptoms. One patient, however, showed values higher than the norm, for six subscores before implantation and for eight subscores before explantation. A significant improvement was found in both the overall psychological distress level (tGSI) and the severity of reported symptoms (tPDSI) at the final visit, compared to those at the study start. The number of self-reported symptoms (tPST) was not significantly altered. CONCLUSION: In the first ongoing pilot trial with an active, cable-bound subretinal implant, we found that trial participation and the implant procedure and subsequent testing did not have any adverse effects on the participants' emotional wellbeing. Their distress generally improved during study participation, rather than showing signs of decreased wellbeing.
    Albrecht von Graæes Archiv für Ophthalmologie 11/2012; · 1.93 Impact Factor
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    ABSTRACT: BACKGROUND: Replacing the function of visual pathway neurons by electronic implants is a novel approach presently explored by various groups in basic research and clinical trials. The novelty raises unexplored methodological aspects of clinical trial design that may require adaptation and validation. METHODS: We present procedures of efficacy and safety testing for subretinal visual implants in humans, as developed during our pilot trial 2005 to 2009 and multi-centre clinical trial since 2010. RESULTS: Planning such a trial requires appropriate inclusion and exclusion criteria. For subretinal electronic visual implants, patients with photoreceptor degeneration are the target patient group, whereas presence of additional diseases affecting clear optic media or the visual pathway must be excluded. Because sham surgery is not possible, a masked study design with implant power ON versus OFF is necessary. Prior to the efficacy testing by psychophysical tests, the implant's technical characteristics have to be controlled via electroretinography (ERG). Moreover the testing methods require adaptation to the particular technology. We recommend standardised tasks first to determine the light perception thresholds, light localisation and movement detection, followed by grating acuity and vision acuity test via Landolt C rings. A laboratory setup for assessing essential activities of daily living is presented. Subjective visual experiences with the implant in a natural environment, as well as questionnaires and psychological counselling are further important aspects. CONCLUSIONS: A clinical trial protocol for artificial vision in humans, which leads a patient from blindness to the state of very low vision is a challenge and cannot be defined completely prior to the study. Available tests of visual function may not be sufficiently suited for efficacy testing of artificial vision devices. A protocol based on experience with subretinal visual implants in 22 patients is presented that has been found adequate to monitor safety and efficacy.
    Clinical and Experimental Optometry 11/2012; · 1.26 Impact Factor
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    ABSTRACT: PURPOSE: To compare visual acuities estimated by three methods of visual evoked potential (VEP) recordings to those obtained by two subjective measures [ETDRS and FrACT (Freiburg acuity test)]. METHODS: Ten healthy subjects, aged between 26 and 67 years (mean 43.5), were examined. Best-corrected acuity determined by the ETDRS was between 0.03 and -0.3 logMAR (mean -0.06). Sweep VEPs (sweepVEP), pattern appearance VEPs (pappVEP) and steady-state VEPs (ssVEP) were recorded with two electrode placements (10-20 and Laplace) with best optical correction and with artificially degraded vision using five Bangerter occlusion foils, reducing acuity to about 0.1, 0.22, 0.52, 0.7 and 1.0 logMAR (0.8, 0.6, 0.3, 0.2 and 0.1 decimal scale). Two runs were performed. RESULTS: ETDRS and FrACT acuities showed good agreement, even though ETDRS seemed to underestimate acuity compared with FrACT at higher acuities. Laplace derivation did not improve any of the VEP-estimated acuities over the 10-20. SweepVEP tended to overestimate lower FrACT acuities, but showed good repeatability. PappVEP placed FrACT acuities into correct or neighboring categories in 87 % of cases. Average ssVEP acuity showed little difference to those of FrACT but variance was larger. ROC analysis for typical clinical application showed good performance for all three methods. CONCLUSIONS: The two subjective measurements of acuities are well correlated. Under the conditions of our experiment, sweepVEP results were less variable and had a better repeatability than ssVEP acuities, whose analysis, in contrast to sweepVEP, can be automated. PappVEP estimates, however, offer a viable alternative, that is, quicker but of lower performance regarding the detection of low acuity thresholds. All methods had a good performance regarding minimum acuity detection if an average of two runs is used.
    Documenta Ophthalmologica 11/2012; · 1.11 Impact Factor
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    ABSTRACT: To investigate rod and cone function and disease mechanisms in patients with KCNV2 retinopathy. Psychophysical examinations as well as detailed electrophysiological examinations with Ganzfeld and multifocal electroretinogram (ERG) were performed to study response dynamics. Additionally, fundus photography, autofluorescence imaging and spectral domain OCTs were carried out for morphological characterization. Molecular genetic analysis revealed compound heterozygosity in five patients and homozygosity for the KCNV2 gene in one patient. The mutations resulted in complete absence of Kv8.2 subunits in three patients (no protein group, NOP), while the other three patients expressed mutant Kv8.2 subunits resulting in altered Kv2.1/Kv8.2 heteromeric or residual Kv2.1 homomeric potassium channel function (altered protein group, ALP). Although more advanced morphological changes were visible in the NOP group, a clear functional difference between the two groups could not be observed. All patients showed characteristic dynamics of the b-wave intensity-response function, however, scotopic b-wave response amplitudes were within normal limits. We also observed severely reduced oscillatory potentials. A specific genotype-phenotype correlation in retinal function could not be demonstrated. KCNV2 mutations cause a unique form of retinal disorder illustrating the importance of K(+)-channels for the resting potential, activation and deactivation of photoreceptors, while phototransduction remains unchanged. The reduced oscillatory potentials further suggest an altered function of the inner retina. Besides the characteristically steep amplitude-versus-intensity relationship, flicker responses at intermediate frequencies (5-15 Hz) are significantly reduced and shifted in phase.
    PLoS ONE 10/2012; 7(10):e46762. · 3.53 Impact Factor

Publication Stats

9k Citations
1,367.18 Total Impact Points

Institutions

  • 1994–2014
    • University of Tuebingen
      • • Institute for Ophthalmic Research
      • • Institute of Musicology
      • • Institute of Physical and Theoretical Chemistry
      Tübingen, Baden-Württemberg, Germany
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
  • 2013
    • Universitätsklinikum Erlangen
      • Department of Ophthalmology
      Erlangen, Bavaria, Germany
  • 1970–2013
    • Universitätsklinikum Tübingen
      • Division of Experimental oncology
      Tübingen, Baden-Württemberg, Germany
  • 2009
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2006–2009
    • University of Zurich
      Zürich, Zurich, Switzerland
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 2004–2007
    • Medical University of Lublin
      • Department of Toxicology (Pharmacy)
      Lyublin, Lublin Voivodeship, Poland
    • Forschungszentrum Jülich
      Jülich, North Rhine-Westphalia, Germany
  • 2002
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 2001
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
  • 1999
    • Universität Stuttgart
      • Institute of Physics
      Stuttgart, Baden-Wuerttemberg, Germany
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • Hohenheim University
      • Institute of Biological Chemistry and Nutrition Sciences
      Stuttgart, Baden-Wuerttemberg, Germany
  • 1997
    • Otto-von-Guericke-Universität Magdeburg
      • Clinic for Ophthamology
      Magdeburg, Saxony-Anhalt, Germany
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1995
    • University Hospital Essen
      Essen, North Rhine-Westphalia, Germany
  • 1993
    • Universitätsmedizin Göttingen
      • Department of Clinical Neurophysiology
      Göttingen, Lower Saxony, Germany
  • 1992
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 1989
    • University of Cambridge
      Cambridge, England, United Kingdom