Eberhart Zrenner

Medical University of Lublin, Lyublin, Lublin Voivodeship, Poland

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Publications (551)1533.78 Total impact

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    ABSTRACT: PurposeMutations in the RLBP1 gene encoding the cellular retinaldehyde-binding protein (CRALBP) cause autosomal recessive progressive retinopathy, such as retinitis punctata albescens (RPA), Bothnia-type dystrophy (BD), Newfoundland rod-cone dystrophy (NFRCD), retinitis pigmentosa (RP) and fundus albipunctatus (FA). We present the clinical heterogeneity and genetic findings of seven patients from five families with RLBP1 mutations, including three novel mutations.Methods Seven patients underwent complete ophthalmological examination including psychophysical tests (visual acuity, colour vision, visual field, dark adaptation) and electrophysiology (Ganzfeld and multifocal ERG). Additionally, fundus photography, autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) recordings were performed. Genomic DNA was analysed by high-throughput sequencing for all RP-related genes in a diagnostic set-up.ResultsThe patients presented with variable phenotypes, including RPA, BD, RP and a mild form of NFRCD. No detectable or severely depressed responses in electrophysiological examinations were seen in all cases. Visual field constriction was variable among individuals. Severely reduced visual acuity was only observed in the patient presenting with BD. The other patients retained mild to moderate reduction of visual function. Despite the morphological differences, central retinal thinning – as a common feature – could be observed.Conclusions The fact that different mutations in RLBP1 are correlated with quite different morphological and functional characteristics outlines the complexity of the protein. Identifying new mutations and comparing the different phenotypes may help to better understand the function of the protein and the consequences in pathological changes that involve RPE and choroid.
    Full-text · Article · Oct 2014 · Acta ophthalmologica
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    ABSTRACT: Background: To restore vision in patients with retinitis pigmentosa, several types of electronic devices have been developed to stimulate neurons at different levels along the visual pathway. Subretinal stimulation of the retina with the Retina Implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) has been demonstrated to provide useful vision in daily life. Here we evaluated the safety of this device. Methods: An interventional, prospective, multi-center, single-arm study was conducted in patients with retinitis pigmentosa with the Retina Implant Alpha IMS. The results from the first nine patients of a single center regarding safety of the device are reported. Any untoward medical occurrence related or unrelated to the tested device was documented and evaluated. Results: Nine adult subjects were included in the study at the Tübingen site. Seventy-five adverse events occurred in total, and 53 affected the eye and its adnexa. Thirty-one ocular adverse events had a relationship to the implant that was classified as "certain" while 19 had a probable or possible relationship; three had no relationship to the implant. Thirty-nine ocular adverse events resolved without sequelae, two resolved with sequelae, 11 remained unresolved, and in one the status was unknown. The intensity of ocular adverse events was mild in the majority of cases (n = 45), while six were of moderate and two of severe intensity. There was no non-ocular adverse event with certain relationship to the device. One subject lost light perception (without light localization) in her study eye. Conclusions: In conclusion, this prospective study, "Safety and Efficacy of Subretinal Implants for Partial Restoration of Vision in Blind Patients," shows that the Retina Implant Alpha IMS is an option for restoring vision using a subretinal stimulation device with a clinically acceptable safety profile.
    No preview · Article · Sep 2014 · Albrecht von Graæes Archiv für Ophthalmologie
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    ABSTRACT: During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with remnant cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca(2+) imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs), we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from interneurons such as HCs and/or possibly interplexiform cells. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type) cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates) the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells.
    Full-text · Article · Sep 2014 · Frontiers in Neural Circuits
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    ABSTRACT: Recently, reports have been published on the effectiveness of electrical stimulation in patients and experimental animal models with neurodegenerative ocular disease.
    Preview · Article · Jun 2014 · Der Ophthalmologe
  • H P Zenner · M Pfister · N Friese · E Zrenner · M Röcken
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    ABSTRACT: Objectives: To evaluate present options for the indication of cochlear implants (CI) and new forms of treatment for head and neck cancer, melanomas and basal cell carcinomas, with emphasis on future perspectives. Methods: A literature search was performed in the PubMed database. Search parameters were "personalized medicine", "individualized medicine" and "molecular medicine". Results: Personalized medicine based on molecular-genetic evaluation of functional proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming increasingly important for the indication of CI in the context of infant deafness. Determination of HER2/EGFR mutations in the epithelial growth factor receptor (EGFR) gene may be an important prognostic parameter for therapeutic decisions in head and neck cancer patients. In basal cell carcinoma therapy, mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly influence the indication of therapeutic Hedgehog inhibition, e.g. using small molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required for specific molecular therapy of metastasizing melanomas. The significant advances in the field of specific molecular therapy are best illustrated by the availability of the first gene therapeutic procedures for treatment of RPE65-induced infantile retinal degradation. Conclusion: The aim of personalized molecular medicine is to identify patients who will respond particularly positively or negatively (e.g. in terms of adverse side effects) to a therapy using the methods of molecular medicine. This should allow a specific therapy to be successfully applied or preclude its indication in order to avoid serious adverse side effects. This approach serves to stratify patients for adequate treatment.
    No preview · Article · Jun 2014 · HNO
  • Eberhart Zrenner · Konrad Tomaszewski · Julia Hamlin · Gary Layton · Nolan Wood
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    ABSTRACT: Purpose: To investigate the effects, and their reversibility, of multiple oral voriconazole doses on a variety of visual tests in healthy male volunteers. Methods: Single-center, double-blind, randomized, placebo-controlled, parallel-group study in 36 volunteers who received voriconazole (n=18, 400 mg every 12 h on day 1, then 300 mg every 12 h for 27.5 days) or matched placebo (n=18). Electroretinograms (ERGs) and ophthalmological examinations were performed at screening, throughout the study and at follow-up. Results: Fifteen (83.3%) volunteers treated with voriconazole experienced ≥1 treatment-related visual adverse events (AEs); these included enhanced visual perceptions, blurred vision, color vision changes and photophobia. No serious AEs were reported. Voriconazole reduced from baseline scotopic maximal a- and b-wave amplitude, shortened implicit time and decreased oscillatory potential amplitude compared with placebo. Under photopic conditions, the 30-Hz flicker response amplitude was significantly reduced and was accompanied by a slight but nonsignificant prolongation of peak time. These effects did not progress in degree over the treatment period, and mean changes from baseline in ERG parameters were similar to placebo by day 43 (14 days after end of treatment). In the first week, color vision discrimination was impaired in the tritan axis, although this resolved by end of treatment and was similar to placebo by day 43. Mean deviation in the static visual field indicated increased sensitivity following voriconazole treatment, correlating with decreased amplitude in conjunction with shortened implicit time. Conclusions: Effects of voriconazole on altered visual perception, ERG, color vision and static visual field thresholds are nonprogressive over a treatment period and reversible. It is hypothesized that voriconazole has a pharmacological effect on rod and cone pathways including a possible mechanism of disinhibition that reversibly puts the retina in a more light-adapted state and leads to increased relative contrast sensitivity.
    No preview · Article · Jun 2014 · Ophthalmic Research
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    ABSTRACT: The mechanisms of neuronal cell death are still only poorly understood, which has hindered the advancement of therapies for many currently untreatable neurodegenerative diseases. This calls for the development of new methods which reveal critical molecular mechanisms of the cell death machinery with both high sensitivity and cellular resolution. Using animal models for hereditary neurodegeneration in the retina, we have developed or adapted different biochemical assays to determine the enzymatic activities of calpain, poly-ADP-ribose-polymerase (PARP), and histone deacetylase (HDAC) directly and in situ. Additionally, the enzymatic activity of cGMP-dependent protein kinase (PKG) was assessed indirectly using in situ immunohistological techniques to detect PKG-activity-dependent products. Combining these assays with in situ cell death markers revealed close temporospatial correlations, suggesting causal connections between the PKG, HDAC, PARP and calpain activities and neuronal cell death. Using different pharmacological and genetic manipulations, causality could indeed be demonstrated. Surprisingly, the often dramatic rises in metabolic activities were not matched by corresponding increases in expression, high-lighting the importance of analyses of protein activities at the cellular level. The above mentioned studies identified a number of metabolic processes previously unknown to be involved in inherited retinal degeneration. Comparing different animal retinal degeneration models uncovered striking similarities in enzymatic activities, suggesting a generality of the destructive pathways. Taken together, these findings provided a number of novel targets for neuroprotection and as such opened up new perspectives for the therapy of hereditary neurodegeneration in the retina and possibly other parts of the central nervous system.
    No preview · Article · Jun 2014 · Current Medicinal Chemistry
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    ABSTRACT: Aims: High altitude provides environmental conditions with dry air and cold temperatures that may facilitate the development of dry eye symptoms. This study investigated, for the first time, the quality of the tear film during high altitude exposure in healthy subjects. This study is related to the Tübingen High Altitude Ophthalmology (THAO) study. Methods: Tear film osmolarity (TFO), tear film breakup time (TBUT), and Schirmer I and II were used to assess tear film properties under standardized conditions in 14 healthy subjects on day 1, 2, and 4 during exposure to high altitude at the Capanna Margherita (CM; 4559 m, Italy) compared to baseline measurements in Tübingen (341 m, Germany) before (BL1) and after (BL2) exposure. Results: Upon arrival at CM, a significant increase in intra-individual TFO (309.1 ± 19.3, 332.2 ± 24.1, 335.5 ± 28.7, 329.7 ± 19.0, and 308.5 ± 15.3 mOsms/L at BL1, day 1, 2, 4, and BL2, respectively) and a significant decrease of TBUT (11.2 ± 5.2, 7.3 ± 5.2, 7.2 ± 11.6, 4.5 ± 2.3, and 8.7 ± 4.6 seconds at BL1, day 1, 2, 4, and BL2, respectively) were found. Schirmer test changes at high altitude remained statistically nonsignificant compared to baseline. Comparisons of parameters between BL1 and BL2 showed no statistically significant differences and recordings of right and left eyes for TBUT and Schirmer did not differ significantly on any day measured. Conclusion: High altitude exposure leads to an altered tear film resulting in an increased TFO and a reduced TBUT. These changes were fully reversible after descent. This is of clinical importance to populations living in high altitude areas and to trekkers and mountaineers exposed to high altitude due to their ever-increasing number.
    Full-text · Article · Jun 2014 · High Altitude Medicine & Biology
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    ABSTRACT: Purpose: To compare the phenotype of patients with heterozygous mutation in GUCY2D or GUCA1A causing autosomal dominant cone or cone-rod dystrophies. Methods: Five patients from one family with GUCA1A and nine patients from four families with GUCY2D mutations were included. Psychophysical and electrophysiological examinations were performed to study retinal function. Fundus autofluorescence imaging and spectral domain optical coherence tomography were performed for morphologic characterization. Results: Genetic analysis revealed the mutation c.451C>T (p.L151F) in the GUCA1A family. In the GUCY2D group, c.2512C>T (p.R838C) was the most frequent (2 families), c.2512C>G (p.R838G) and c.2513G>A (p.R838H) were found in one family each. Visual acuity was reduced to 0.04 to 0.7 in GUCA1A and to 0.014 to 0.5 in patients with GUCY2D. Dark adaptation showed elevated thresholds in the GUCY2D group. Scotopic electroretinography revealed a tendency to a more affected rod function in the GUCY2D group. Photopic electroretinography showed residual or absent responses in both groups. Fundus alterations were confined to the macula in both groups. Conclusion: GUCA1A and GUCY2D mutations are both accompanied by similar pattern of generalized cone dysfunction with a tendency to less involvement of the rod photoreceptors and a less severe phenotype in patients with GUCA1A.
    Full-text · Article · May 2014 · Retina (Philadelphia, Pa.)
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    ABSTRACT: As impaired S-cone function has been reported psychophysically this study assessed S-cone function during high altitude exposure using electroretinography (ERG) and investigated a possible association with severity of acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Standard ERG equipment was used (Diagnosys LLC, Cambridge, UK) with special protocol settings to extract S-cone function. Twelve subjects were analyzed in the current study and examinations were performed in Tübingen, Germany (341 m) as baseline and thereafter at the Capanna Margherita, Italy (4.559 m) at high altitude. Results were compared using a paired t-test. Correlations between ERG measurements and oxygen saturation (SpO2), heart rate (HR) and scores of acute mountain sickness (AMS-C and LL) were calculated using Pearson’s correlation coefficients. Amplitudes of S-cone b-waves decreased significantly at high altitude (p = 0.02). No significant changes were observed for implicit times of b-waves (p = 0.63), a-waves (p = 0.75) or for a-wave amplitudes (p = 0.78). The incidence of AMS was 50% at high altitude according to AMS-C and LL scores (AMS-C⩾0.7 and LL⩾5). Heart rate increased to 84±10 min-1 and SpO2 decreased to 71.9±5.7% at high altitude. No significant correlation was found between S-cone ERG parameters and SpO2, HR, AMS-C and LL. For the first time our study defines a significant impairment of S-cone function at high altitude time using objective state of the art examination methods. No correlation between the functional impairment of S-cones and levels of AMS was detected.
    No preview · Article · Apr 2014 · Vision research
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    ABSTRACT: This study aimed to quantify the pupillary light reaction during high altitude exposure using the state of the art Compact Integrated Pupillograph (CIP) and to investigate a potential correlation of altered pupil reaction with severity of acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Parameters of pupil dynamics (initial diameter, amplitude, relative amplitude, latency, constriction velocity) were quantified in 14 healthy volunteers at baseline (341 m) and high altitude (4559 m) over several days using the CIP. Scores of AMS, peripheral oxygen saturation and heart rate were assessed for respective correlations with pupil dynamics. For statistical analysis JMP was used and data are shown in terms of intra-individual normalized values (value during exposure/value at baseline) and the 95% confidence interval for each time point. During high altitude exposure the initial diameter size was significantly reduced (p<0.05). In contrast, the amplitude, the relative amplitude and the contraction velocity of the light reaction were significantly increased (p<0.05) on all days measured at high altitude. The latency did not show any significant differences at high altitude compared to baseline recordings. Changes in pupil parameters did not correlate with scores of AMS. Key parameters of the pupillary light reaction are significantly altered at high altitude. We hypothesize that high altitude hypoxia itself as well as known side effects of high altitude exposure such as fatigue or exhaustion after ascent may account for an altered pupillogram. Interestingly, none of these changes are related to AMS.
    Full-text · Article · Feb 2014 · PLoS ONE
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    ABSTRACT: The current study aimed to investigate retinal function during exposure to normobaric hypoxia. Standard Ganzfeld ERG equipment (Diagnosys LLC, Cambridge, UK) using an extended ISCEV protocol was applied to explore intensity-response relationship in dark- and light- adapted conditions in 13 healthy volunteers (mean age 25 ± 3 years). Baseline examinations were performed under atmospheric air conditions at 341 meters above sea level (FIO2 of 21 %), and were compared to hypoxia (FIO2 of 13.2 %) by breathing a nitrogen-enriched gas mixture for 45 min. All subjects were monitored using infrared oximetry and blood gas analysis. The levels of PaCO2 changed from 38.4 ± 2.7 mmHg to 36.4 ± 3.0 mmHg, PaO2 from 95.5 ± 1.9 mmHg to 83.7 ± 4.6 mmHg, and SpO2 from 100 ± 0 % to 87 ± 4 %, from baseline to hypoxia respectively. A significant decrease (p < 0.05) was found for saturation amplitude of the dark-adapted b-wave intensity-response function (Vmax), dark-adapted a- and b-wave amplitudes of combined rod and cone responses (3 and 10 cd.s/m(2)), light-adapted b-wave amplitudes of single flash (3 and 10 cd.s/m(2)), and flicker responses (5-45 Hz) during hypoxia compared to baseline, without changes in implicit times. The a-wave slope of combined rod and cone responses (3 and 10 cd.s/m(2)) and the oscillatory potentials were significantly lower during hypoxia (p < 0.05). A isolated light-adapted ON response (250 ms flash) showed a reduction of amplitudes at hypoxia (p < 0.05), but no changes were observed for the OFF response. The results show significant impairment of retinal function during simulated normobaric short-term hypoxia affecting specific retinal cells of rod and cone pathways.
    No preview · Article · Nov 2013 · Albrecht von Graæes Archiv für Ophthalmologie
  • Eberhart Zrenner
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    ABSTRACT: There is no approved cure for blindness caused by degeneration of the photoreceptor cells of the retina. However, there has been encouraging progress with attempts to restore vision using microelectronic retinal implant devices. Yet many questions remain to be addressed. Where is the best location to implant multielectrode arrays? How can spatial and temporal resolution be improved? What are the best ways to ensure the safety and longevity of these devices? Will color vision be possible? This Perspective discusses the current state of the art of retinal implants and attempts to address some of the outstanding questions.
    No preview · Article · Nov 2013 · Science translational medicine
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    ABSTRACT: Purpose: An active microelectronic subretinal implant, developed to replace the photoreceptive function in hereditary degenerations of the outer retina, has been applied in a pilot and clinical study in patients with end-stage retinal degeneration. Methods: The study population comprised 20 blind patients, all of whom lost vision as result of a hereditary retinal disease. An active visual implant was placed surgically within the subretinal space of each patient: subfoveal placement in eight patients (group 1) and parafoveal placement in 12 (group 2). Standardized low-vision tests, including light perception, light localization, movement detection, grating acuity, and visual acuity by Landolt C-rings, were used under masked, randomized implant-OFF and implant-ON conditions. For the chip-mediated vision functional results of both subject groups were compared. Results: Three of 20 patients were excluded from analysis because of surgical or technical implant issues. Among patients with nonfoveal placement of the implant, 80% could perceive light, 10% recognized location, and 10% correctly distinguished stripe patterns up to a resolution of 0.33 cycles/degree. No nonfoveal placement patient passed the motion or Landolt C-ring tests. When the implant was placed subfoveally, 100% of patients could perceive light and determine light localization, 75% could resolve motion up to 35°/s, 88% correctly distinguished stripe patterns up to a resolution of 3.3 cycles/degree, and 38% passed a Landolt C-ring test with a decimal visual acuity of up to 20/546 (logMAR 1.43). Conclusions: Subfoveal placement of active subretinal visual implants allows superior measurable outcomes compared to para- or nonfoveal placement locations. (ClinicalTrials.gov numbers, NCT01024803, NCT00515814.).
    No preview · Article · Oct 2013 · Investigative ophthalmology & visual science
  • Katarina Stingl · E Zrenner
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    ABSTRACT: Degenerations of the outer retina are hereditary diseases leading to significant loss of vision. Several concepts of active electrical stimulation of the remaining retinal network resulted in the development of retinal visual implants and prosthetic vision. Subretinal and epiretinal visual implants are currently the leading approaches in restoring functional vision in blind humans with retinitis pigmentosa or other outer retinal degenerations. This review gives a short overview about the principles, advantages, limitations and vision outcome of the up-to-date published artificial vision by electronic visual implants, as well as their known biocompatibility and safety issues. © 2013 S. Karger AG, Basel.
    No preview · Article · Sep 2013 · Ophthalmic Research
  • Paul Werginz · Heval Benav · Joerg Encke · Eberhart Zrenner · Frank Rattay
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    ABSTRACT: The newest generation of retinal implants show that restoration of vision for blind patients is generally possible. However, there are still many obstacles to overcome to achieve a higher quality of artificial vision. A crucial factor in the used micro-photodiode-arrays is the shape and size of the stimulating elements. This study compares two different electrode shapes and the outcome during subretinal stimulation, respectively. Monopolar (disc) and dipolar (ring) electrodes were modeled with a finite element approach. With the calculated electric potentials we simulated the response of target cells to electric stimulation. Additionally, we concentrated on power consumption/charge limit in the modeled electrode configurations.
    No preview · Article · Sep 2013 · Biomedizinische Technik/Biomedical Engineering
  • Jörg Encke · Heval Benav · Paul Werginz · Eberhart Zrenner · Frank Rattay
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    ABSTRACT: Neuronal compartment models are a basic and often used method to investigate the effect of electrical stimulation on the cell. As the outcome of the model heavily depends on the cells morphology and its position relative to the electrode, a realistic representation of the cell structure and its variations is of great importance. A method is presented which allows the quick and easy creation of a three dimensional neuron morphology on the basis of a single two dimensional image. Basic properties of this morphology like local diameters, cell size or the amount of branching can easily be changed.
    No preview · Article · Sep 2013 · Biomedizinische Technik/Biomedical Engineering
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    ABSTRACT: Purpose In vision research as well as in other research disciplines, like psychology or psychophysiology, there is often a need for presenting visual stimuli and for registration of a physiological responses, like the pupil diameter, to them. Commonly, this is realized by making use of notebooks or desktop computers, therefore, wasting resources and energy. Here, we present a new platform for vision research based on the Raspberry Pi (RPi), an inexpensive, yet powerful system-on-a-chip (SoC). Methods The ARM based RPi, running up to 1GHz with 512MB RAM and offering interfaces like HDMI, RJ-45, USB and GPIO at a price of $35 only, is a convinient basis for vision research. We took a recently published study dealing with pupil responses to pictures of light sources as draft to test its suitabilty for this usage. One RPi was used for controlling stimulus presentation, a second one for measuring the pupil diameter based on a video stream. The software was implemented using Java on a debian linux. Results Due to the limited memory and processor performance, the framerate was restricted to about 20fps. However, it allowed for the recording of changes in the pupil diameter in response to the presented stimuli. We successfully comprehended a previous study, and thus showed that the RPi is a serious and cheap alternative to using notebooks or desktop computers for vision research. Conclusion In spite of its size, the RPi provides surprising high performance. Based on open-source software, applications can be implemented in languages like Java or Python, leveraging existing software packages. After the advent of the Raspberry Pi, similar devices became available, providing even more performance for low prices.
    No preview · Article · Aug 2013 · Acta ophthalmologica
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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.
    Full-text · Article · Jun 2013 · Journal of Neurochemistry
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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 (CCT) and the geometry of the anterior chamber angle (ACA). This work is related to the Tübingen High Altitude Ophthalmology study. Methods: Anterior segment spectral domain optical coherence tomography was used to quantify changes in individual corneal layers and to study 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 (341 m) and altitude (4559 m) for respective correlations. Results: Longitudinal analysis revealed a significant (P < 0.05) increase of CCT during altitude exposure (CCT(baseline) = 539.27 ± 32.30 μm; CCT(day1) = 558.87 ± 29.39 μm; CCT(day3) = 567.17 ± 33.40 μm; mean ± SD) due to stromal edema. 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 day 1 was 64% followed by a decrease in AMS scores over time spent at high altitude; while AMS correlated significantly with stromal edema formation just after arrival (r = 0.71; P = 0.01), no correlation was found on day 3 (r = 0.05; P = 0.87); no correlations were found for vital parameters. Conclusions: Significant stromal edema 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.
    No preview · Article · Jun 2013 · Investigative ophthalmology & visual science

Publication Stats

14k Citations
1,533.78 Total Impact Points


  • 2015
    • Medical University of Lublin
      Lyublin, Lublin Voivodeship, Poland
  • 1990-2015
    • University of Tuebingen
      • • Institute for Ophthalmic Research
      • • Institute of Physical and Theoretical Chemistry
      Tübingen, Baden-Württemberg, Germany
  • 1970-2013
    • Universitätsklinikum Tübingen
      • Division of Experimental oncology
      Tübingen, Baden-Württemberg, Germany
  • 2010
    • Johns Hopkins University
      • Wilmer Eye Institute
      Baltimore, Maryland, United States
  • 1998-2010
    • Universität Regensburg
      • Department of Ophthalmology
      Ratisbon, Bavaria, Germany
  • 1994-2008
    • University of Cologne
      • Institute of Human Genetics
      Köln, North Rhine-Westphalia, Germany
  • 2001
    • University Hospital Zürich
      Zürich, Zurich, Switzerland
  • 1999
    • Universität Stuttgart
      • Institute of Physics
      Stuttgart, Baden-Wuerttemberg, Germany
    • Hohenheim University
      • Biochemistry and Nutrition Unit
      Stuttgart, Baden-Württemberg, Germany
  • 1997
    • Otto-von-Guericke-Universität Magdeburg
      • Clinic for Ophthamology
      Magdeburg, Saxony-Anhalt, Germany
  • 1995
    • Stanford Medicine
      • Department of Ophthalmology
      Stanford, California, United States
  • 1993-1995
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1992
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 1989
    • Augenklinik am Marienplatz
      München, Bavaria, Germany
  • 1986-1989
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 1979-1981
    • Columbia University
      New York City, New York, United States