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E Zrenner

Publications and source records attributed to E Zrenner.

At least 19 recordsLinked to original sources
PubMed2006

Kynurenic acid synthesis in bovine retinal slices--effect of glutamate agonists.

The purpose of the present study was to investigate the effect of glutamate agonists upon kynurenic acid (KYNA) production in bovine retinal slices. Quantitative analysis of newly synthesized KYNA was carried out using an HPLC system and detected fluorimetrically. Glutamate at the concentration of 0.01, 0.1 and 1 mM reduced KYNA synthesis in the retinal slices to 70% (p < 0.05), 35% (p < 0.01) and 23% (p < 0.001), respectively. The concentration of glutamate reducing production of KYNA by 50% (IC(50)) was 0.035 mM (0.02-0.06). Aspartate at the concentration of 0.01, 0.1 and 1 mM lowered KYNA synthesis in the retinal slices to 80% (p < 0.01), 57% (p < 0.001) and 43% (p < 0.001), respectively. In contrast, kainic acid (up to 5 mM), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (up to 1 mM) and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) (up to 3 mM) turned out to be ineffective in diminishing KYNA synthesis. These data demonstrate that glutamate, aspartate and N-methyl-D-aspartate (NMDA) inhibit KYNA synthesis in bovine retinal slices with different potency.

Animals↗
PubMed2006

[Integrated approach to the promotion of young academics in vision research at a European level].

The European Commission predicts a dramatic dearth of researchers and doctors in the near future. At the same time, highly qualified and motivated human resources form the only guarantee for further development of scientific knowledge for research and clinical application. This situation calls for an integrated approach to the promotion of young academics in vision research at a European level. The Marie Curie Program of the European Union is an ideal tool, which can be used particularly efficiently in vision research to promote international networking and dedicated advancement of young academics. The exemplary chances and opportunities of this strategy can be demonstrated by six specific measures of the University Eye Hospital in Tübingen. In particular, strictly defined medical areas will need to fully exploit their innovation potential in the future in order to secure their position in the global research area or even to expand it. New organizational concepts and long-term career options as well as a clear commitment to cutting-edge performance are the prerequisites for effective promotion of young academics.

Academic Medical Centers↗
PubMed2006

[The European Vision Institute. Opening up new frontiers?].

The European Vision Institute EEIG (EVI) creates a new legal entity based on Community law to facilitate and encourage cross-border co-operation in vision research. Its major objectives are to conduct and support research, training, health information dissemination and other programmes with respect to blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight and the special health problems and requirements of the blind and visually disabled. EVI aims to foster centres in the EU in capacity building for innovative projects, to increase the flexibility, attractiveness and competitiveness of research careers, especially for young researchers. In addition, EVI will serve to co-ordinate activities with patient organisations and to build a pan-European platform for clinical trials.

Academies and Institutes↗
PubMed2006

[Establishing ophthalmology in the research framework programs of the European Union].

The framework programmes (FP) of the European Commission have substantially contributed to the funding of research within the European countries. The contribution of the funding provided by the EU relative to the funding available on the national level has steadily increased. European ophthalmology and vision research has benefited from this support provided by the EU. This review introduces the European funding policies and the European Research Area (ERA) and provides a list of all projects in ophthalmology and vision research that have been funded within FP1 to FP6. As an example for new instruments within FP6, Integrated Projects, the EVI-GENORET project is introduced. Finally an outlook for FP7 is provided.

Biomedical Research↗
PubMed2005

A genetic perspective on myopia.

Myopia is a refractive error of the eye that has a significant socioeconomic impact due to its increasing prevalence and the fact that it causes visual impairment. Its aetiology is complex and is likely to involve the interaction of environmental and genetic influences. Tight environmental influence is exemplified by defocus-induced myopia produced in animal models, while genetic factors predominate in familial occurrence of myopia with a Mendelian inheritance pattern. The involvement of numerous mediators, such as cytokines, neurotransmitters and transcription factors, in myopia development has been indicated through various lines of investigation, particular interest focussing on scleral extracellular matrix proteins and developmental genes of the eye. As high-throughput technology for large-scale genotyping and RNA expression analysis enters the field of myopia research, a productive avenue will open up for deciphering the aetiological heterogeneity of myopia and the biological pathways underlying its development.

Animals↗
PubMed2005

[Status of the subretinal implant project. An overview].

The development of a subretinal prosthesis has come to a stage where human trials are forthcoming. Subretinal prostheses are designed to replace degenerated photoreceptors in diseases such as retinitis pigmentosa or age-related macular degeneration. Microphotodiode arrays are implanted between retinal pigment epithelium and retina. Our group has collected convincing evidence for the principle feasibility of a subretinal prosthesis. Animal experiments have shown that subretinal electrical stimulation can successfully elicit spatially ordered responses in the visual cortex; visual acuity is estimated to reach 0.25 degrees of visual angle. Histological long-term examinations have demonstrated that the retina tolerates a subretinal implant well and also that the implant itself sustains the ocular environments. Surgical procedures have been successfully developed to implant complex subretinal devices.

Animals↗
PubMed2005

Novel rhodopsin mutations and genotype-phenotype correlation in patients with autosomal dominant retinitis pigmentosa.

AIM: To identify novel or rare rhodopsin gene mutations in patients with autosomal dominant retinitis pigmentosa and description of their clinical phenotype. METHODS: The complete rhodopsin gene was screened for mutations by DNA sequencing in index patients. Mutation specific assays were used for segregation analysis and screening for controls. Eight patients from five families and their relatives were diagnosed with autosomal dominant retinitis pigmentosa (adRP) by means of clinical evaluation. RESULTS: Mutation screening identified five different rhodopsin mutations including three novel mutations: Ser176Phe, Arg314fs16, and Val20Gly and two missense mutations, Pro215Leu and Thr289Pro, that were only reported once in a mutation report. Electrophysiological and psychophysical testings provide evidence of an impaired rod system with additionally affected cone system in subjects from each genotype group. Visual function tended to be less affected in subjects with the Arg314fs16 and Val20Gly mutations than in the Ser176Phe phenotype. In contrast, Pro215Leu and Thr289Pro mutations caused a remarkably severe phenotype. CONCLUSION: The ophthalmic findings support a correlation between disease expression and structural alteration: (1) extracellular/intradiscal Val20Gly and cytoplasmic Arg314fs16 mutation-mild adRP phenotype; (2) Ser176Phe mutation-"mostly type 1" disease; (3) predicted alteration of transmembrane domains TM V and TM VII induced by Pro215Leu and Thr289Pro-severe phenotype. However, variation of phenotype expression in identical genotypes may still be a typical feature of RHO mutations.

Adolescent↗
PubMed2004

[Introduction to the topic of functional assessment of sporadic visual field defects].

We present the new recommendation released by the Commission of the German Ophthalmologic Society on evaluation of sporadic visual field defects, which is based on the principle of the Estermann field test. The purpose of the recommendation is to ensure quality assurance and legal certainty in assessment of sporadic visual field defects by field evaluation with a point system.

Disability Evaluation↗
PubMed2002

Stereotactic fractionated irradiation of optic nerve sheath meningioma: a new treatment alternative.

BACKGROUND: Primary optic nerve sheath meningioma (ONSM) is a rare but almost invariably blinding tumour when its natural history is observed in a "wait and see" strategy. Surgery has hitherto only been advocated in case of progressive disease involving intracranial structures, as it leads to iatrogenic blindness in the overwhelming majority of cases. Therefore, treatment options bearing lesser risk of functional deterioration are highly desirable, both in cases of intracranial involvement as well as during earlier phases of the disease which are currently generally left untreated. The authors report the outcome of the largest series of patients to date treated by stereotactic fractionated irradiation as a new treatment approach in ONSM at all stages. METHODS: 15 patients (16 nerves) underwent stereotactic fractionated conformal irradiation with a total dose of 54 Gy, using standard fractionation. Main outcome parameters included visual acuity and visual field, as well as three dimensional remission as documented by imaging. RESULTS: Tumour control was confirmed in all 15 patients undergoing stereotactic fractionated conformal irradiation (mean follow up 37 (range 12-71) months). No patient developed functional deterioration during or after treatment. Moreover, visual acuity improved by more than two lines in one patient and the visual field improved in six cases. Visual outcome in the other patients remained unchanged. There were no significant side effects of radiation therapy. CONCLUSION: These data provide convincing evidence that stereotactic fractionated conformal irradiation is an effective treatment option for primary ONSM with minimal treatment related morbidity. It should therefore be considered as therapeutic option both in early stage ONSM where surgery cannot be justified as well as in later stages, where surgery is so far considered the first line approach.

Adolescent↗
PubMed2002

A novel mutation of the RP1 gene (Lys778ter) associated with autosomal dominant retinitis pigmentosa.

BACKGROUND: Besides the three known genes (RHO, RDS/Peripherin, NRL) involved in autosomal dominant retinitis pigmentosa (adRP), a fourth gene, RP1, has been recently identified. Initial reports suggest that mutations in the RP1 gene are the second most frequent cause of adRP. The clinical findings were described in a family with adRP and a novel mutation in the RP1 gene. METHOD: Index patients from 15 independent families with adRP in which RHO mutations had been excluded in previous examinations were screened for mutations in the RP1 gene by means of direct DNA sequencing. Evaluation of the RP1 phenotype in patients included funduscopy, kinetic perimetry, dark adapted final threshold test, standard electroretinography and, in one case, multifocal electroretinography. RESULTS: One novel nonsense mutation (Lys778ter) in one of these 15 patients was detected. Cosegregation of the mutation with the disease phenotype could be established in the index patient's family. The phenotype comprises variable expression of clinical disease probably including one case of incomplete penetrance, a onset of symptoms beginning in adulthood, and evidence of regionally varying retinal function loss. CONCLUSION: The Lys778ter mutation localises inside the critical region harbouring all mutations described so far. The ophthalmic findings support previous observations that variation of disease expression appears as a typical feature of the RP1 phenotype.

Aged↗
PubMed2001

Presence of kynurenic acid and kynurenine aminotransferases in the inner retina.

Kynurenine aminotransferases (KATs I and II) are pivotal to the synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor antagonist and neuroprotectant. This study is the first to identify KYNA in the rat retina and to examine immunohistochemically the distribution of KAT isoforms. As determined by HPLC, KYNA concentration in the retina was 99.9 +/- 24.6 pmol/g wet wt. Immunohisto- chemical experiments showed that both KATs were present in the retina. KAT I was preferentially localised on Müller cell endfeet while KAT II was expressed in cells within the ganglion cell layer. In conclusion, KYNA is present and synthesised in the inner retina. This may suggest a modulatory role in glutamate-mediated retinal neurotransmission.

Animals↗
PubMed2001

CNGA3 mutations in hereditary cone photoreceptor disorders.

We recently showed that mutations in the CNGA3 gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.

Amino Acid Sequence↗
PubMed2001

OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance.

We and others have shown recently that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein cause autosomal dominant optic atrophy (ADOA) linked to chromosome 3q28-q29. Here we report screening of the OPA1 gene in a sample of 78 independent ADOA families. OPA1 mutations were identified in 25 patients (detection rate 32.1%) including 16 novel mutations. We successfully amplified OPA1 cDNA prepared from leukocyte RNA of three patients, and found the amount of transcripts harboring the Arg366Stop mutation was significantly reduced compared with transcripts derived from the normal chromosome. Analysis of the distribution of OPA1 mutations in ADOA revealed that most missense mutations cluster within the putative GTPase domain, and that there is a preponderance of mutations, which result in premature translation termination. These observations support the notion that haploinsufficiency may represent a major pathomechanism for ADOA. In addition, we identified an ADOA patient who is a compound heterozygote for two OPA1 missense mutations. The fact that this patient is by far more severely affected than her simple heterozygotic parents and siblings implies that at least these OPA1 alleles behave semi-dominantly rather than purely dominantly. Clinical examination revealed considerable variability in disease expression among patients carrying OPA1 mutations and no strict correlation with either the position or the type of mutation.

Adolescent↗
PubMed2001

[Subretinal microphotodiode array as replacement for degenerated photoreceptors?].

A survey is given on the status of developments, concerning a subretinal electronic microphotodiode array that aims at replacing degenerated photoreceptors. Various prototypes have been developed, tested, and implanted in various experimental animals up to 18 months. The fact that electrical responses were recorded from the visual cortex of pigs after electrical stimulation by subretinal electrodes and the fact that responses are also recorded in-vitro in degenerated rat retinae, shows the feasibility of this approach. However, there are a number of open questions concerning the biocompatibility, the long-time stability, and the type of transmitted image to be solved before application in patients can be considered.

Animals↗
PubMed2001

[Histological studies of retinal degeneration and biocompatibility of subretinal implants].

Two basic biological premises determine the success of replacement of degenerated photoreceptors by a technical implant. First, the neuronal network in the residual retina of patients selected for implantation must still be capable of processing technically generated signals. Secondly, the implant itself must be biocompatible with tissue, i.e. it may not itself induce further degeneration. Our studies in animal models with advanced retinal degeneration and with donor retinas of retinitis pigmentosa patients have shown that even after complete destruction of the photoreceptors and long periods of blindness, the inner retina in the macular area remains for the most part histologically intact, and that all neurons are demonstrably still present and capable of successfully transmitting and processing signals. Biocompatibility of subretinal implants was studied in pigs. After 14 months of implantation, histological examination of tissue covering the implant showed that the inner retina was completely intact. There were no signs of histopathologic changes.

Animals↗
PubMed2001

[Physiological functional evaluation of retinal implants in animal models].

Retinal implants can--by electrical stimulation--create visual impressions in people with certain kinds of degenerative retinal diseases (e.g. Retinitis Pigmentosa). Electrically evoked potentials in the retina must be transferred into the visual cortex in an orderly manner, a prerequisite for any kind of form- and movement-perception. In the current developmental stage the difficult investigations are performed in various animal models: isolated retinae of intact chicken and of RCS-rats (a model for Retinitis Pigmentosa), as well as in anesthetised rabbits, pigs and cats with intact retinae. Our investigations show that spatially selective ganglion-cell responses can be recorded following focal electrical stimulation, in healthy and as well in degenerated retinae. Registration of activities in area 17 of the visual cortex demonstrate that electrical retinal stimulation can indeed activate it.

Animals↗