Home About us Contact
|
Home About us Contact | ||
|
|
||
ERG
Kinds of ERG Terms modified by ERG Selected AbstractsProtective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2009Yumiko Yoshida Abstract Background Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy. Methods Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence. Results Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy. Conclusions Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd. [source] The eye of the freshwater prosobranch gastropod Viviparus viviparus: ultrastructure, electrophysiology and behaviourACTA ZOOLOGICA, Issue 1 2006Valery V. Zhukov Abstract We used light and electron microscopy to study the retinal organization of the eye of Viviparus viviparus. Electroretinogram (ERG) recordings were used to investigate the electrophysiological responsiveness to flashes of light of varying intensity and colour, behavioural observations were made of phototactic reactions, and optical measurements and calculations related to the path of light rays in the eye were made. The retina contains principally two types of cells: first, photoreceptor cells with both microvilli and cilia, and second, cells, often strongly pigmented, that are supportive in nature. The ERGs obtained were essentially similar in form, amplitude and duration to those known from other gastropods that have exclusively rhabdomeric photoreceptors. Spectral sensitivity curves closely fitted the absorption spectrum of a rhodopsin-like pigment. The spectral sensitivity peak was at 475 nm. Measurements of the refractive indices of the lens gave values of 1.55 for the outer layer and 1.57 for the lens core. None of the snails tested exhibited a ,defensive reflex' and although no preference between light and dark regions was expressed, we nevertheless argue that, on the basis of optical measurements and calculations, the eye of V. viviparus is well-adapted for seeing under water. Our main conclusion is that in the eye of V. viviparus with its ,mixed photoreceptor' cell type, there is an equal probability for microvilli and cilia to function as principal photoreceptive elements. [source] Evidence for the involvement of purinergic P2X7 receptors in outer retinal processingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Theresa Puthussery Abstract Extracellular ATP mediates fast excitatory neurotransmission in many regions of the central nervous system through activation of P2X receptors. Although several P2X receptor subunits have been identified in the mammalian retina, little is known about the functional role of these receptors in retinal signalling. The purpose of the present study was to investigate whether purinergic P2X7 receptors are involved in outer retinal processing by assessing receptor localization, degradation of extracellular ATP and the effect of functional activation of P2X7 receptors on the electroretinogram (ERG). Using light and electron microscopy, we demonstrated that P2X7 receptors are expressed postsynaptically on horizontal cell processes as well as presynaptically on photoreceptor synaptic terminals in both the rat and marmoset retina. Using an enzyme cytochemical method, we showed that ecto-ATPases are active in the outer plexiform layer of the rat retina, providing a mechanism by which purinergic synaptic transmission can be rapidly terminated. Finally, we evaluated the role of P2X7 receptors in retinal function by assessing changes to the ERG response of rats after intravitreal delivery of the P2X7 receptor agonist benzoyl benzoyl ATP (BzATP). Intravitreal injection of BzATP resulted in a sustained increase (up to 58%) in the amplitude of the photoreceptor-derived a-wave of the ERG. In contrast, BzATP caused a transient reduction in the rod- and cone-derived postreceptoral responses. These results provide three lines of evidence for the involvement of extracellular purines in outer retinal processing. [source] Multiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancersGENES, CHROMOSOMES AND CANCER, Issue 11 2007Wennuan Liu A number of TMPRSS2/ERG fusion transcripts have been reported since the discovery that recurrent genomic rearrangements result in the fusion of TMPRSS2 and ETS family member genes. In this article we present evidence demonstrating that multiple genomic alterations contribute to the formation of various TMPRSS2/ERG transcripts. Using allele-specific analysis of the data generated from the GeneChip 500K SNP array we observed both hemizygous and homozygous deletions occurring at different locations between and within TMPRSS2 and ERG in prostate cancers. The 500K SNP array enabled us to fine map the start and end of each deletion to specific introns of these two genes, and to predict a variety of fusion transcripts, including a new form which was confirmed by sequence analysis of the fusion transcripts in various tumors. We also inferred that translocation is an additional mechanism of fusion for these two genes in some tumors, based on largely diploid genomic DNA between TMPRSS and ERG, and different fusion transcripts produced in these tumors. Using a bioinformatics approach, we then uncovered the consensus sequences in the regions harboring the breakpoints of the deletions. These consensus sequences were homologous to the human Alu-Sq and Alu-Sp subfamily consensus sequences, with more than 80% homology. The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer. © 2007 Wiley-Liss, Inc. [source] Defining the molecular action of HDAC inhibitors and synergism with androgen deprivation in ERG-positive prostate cancerINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Mari Björkman Abstract Gene fusions between prostate-specific, androgen responsive TMPRSS2 gene and oncogenic ETS factors, such as ERG, occur in up to 50% of all prostate cancers. We recently defined a gene signature that was characteristic to prostate cancers with ERG activation. This suggested epigenetic reprogramming, such as upregulation of histone deactylase 1 (HDAC1) gene and downregulation of its target genes. We then hypothesized that patients with ERG -positive prostate cancers may benefit from epigenetic therapy such as HDAC inhibition (HDACi), especially in combination with antiandrogens. Here, we exposed ERG -positive prostate cancer cell lines to HDAC inhibitors Trichostatin A (TSA), MS-275 and suberoylanilide hydroxamic acid (SAHA) with or without androgen deprivation. We explored the effects on cell phenotype, gene expression as well as ERG and androgen receptor (AR) signaling. When compared with 5 other prostate cell lines, ERG -positive VCaP and DuCap cells were extremely sensitive to HDACi, in particular TSA, showing synergy with concomitant androgen deprivation increasing apoptosis. Both of the HDAC inhibitors studied caused repression of the ERG -fusion gene, whereas the pan-HDAC inhibitor TSA prominently repressed the ERG -associated gene signature. Additionally, HDACi and flutamide caused retention of AR in the cytoplasm, indicating blockage of androgen signaling. Our results support the hypothesis that HDACi, especially in combination with androgen deprivation, is effective against TMPRSS2-ERG -fusion positive prostate cancer in vitro. Together with our previous in vivo observations of an "epigenetic reprogramming gene signature" in clinical ERG -positive prostate cancers, these studies provide mechanistic insights to ERG -associated tumorigenesis and suggest therapeutic paradigms to be tested in vivo. © 2008 Wiley-Liss, Inc. [source] Linear and whorled nevoid hypermelanosis associated with developmental delay and generalized convulsionsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2004Ahmad A. Alrobaee MD A 2-year-old Saudi boy was seen in our dermatology clinic with symmetrical, brown, linear macules over the legs, trunk, and arms (Figs 1,3). He was a product of a full-term vaginal delivery following an uneventful first pregnancy in a 22-year-old mother. The birth weight was 2.3 kg. The hyperpigmented macules followed the lines of Blaschko and were noticed a few months after birth; they had enlarged with body growth until the age of 18 months. There was no family history of a similar condition and the boy's parents were unrelated. No blistering or inflammatory changes preceded the hyperpigmentation. The palms, soles, nails, scalp, mucous membranes, and teeth were normal. In addition to the hyperpigmented macules, the patient started to have generalized convulsions at the age of 2 months. Figure 1. Linear hyperpigmented macules following the lines of Blaschko Figure 2. Close up view of the hyperpigmented macules Figure 3. Trunk: Hyperpigmented macules in whorled distribution Physical examination revealed delayed developmental milestones, microphthalmia, depressed nose, and high arched palate with no other abnormalities. Blood tests were normal. Magnetic resonance imaging of the brain showed changes suggestive of a demyelinating process at the parieto-occipital white matter. Echocardiography revealed an atrial septal defect. Electroretinography (ERG), visual evoked potentials (VEP), and auditory evoked potentials (AEP) were normal. Electroencephalogram (EEG) showed multifocal epileptic discharge in the posterior region. A punch skin biopsy taken from the hyperpigmented lesions showed an increase in the melanin content of the basal layer with no incontinence of pigment or melanophages in the dermis. [source] Brain-derived neurotrophic factor shows a protective effect and improves recovery of the ERG b-wave response in light-damageJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Kazuhito Ikeda Abstract We investigated the neuroprotective effects of brain-derived neurotrophic factor (BDNF) and its influence on the functional recovery of the retina following light-induced retinal damage by electroretinogram (ERG). Rats were exposed to constant fluorescent light for 2, 5, 7, or 14 days, then returned to a cyclic light environment for 14 days. The result indicated that BDNF had few effects on the a-wave amplitude, but there was a statistically significant difference in the b-wave amplitudes between BDNF-treated and control eyes from day 0,14 of the recovery period following 2 days of light exposure (p < 0.05). Our findings suggest that BDNF not only protects the retinal neuronal function but also enhances the recovery from retinal light damage. [source] Ocular phenotype in a mouse gene knockout model for infantile neuronal ceroid lipofuscinosisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2006Bo Lei Abstract Mutations in the human protein palmitoyl thioesterase-1 (PPT-1) gene result in an autosomal recessive neurodegenerative disorder designated neuronal ceroid lipofuscinosis (NCL), type CLN1, or infantile NCL. Among the symptoms of the CLN1 disease are accumulation of autofluorescent lysosomal storage bodies in neurons and other cell types, seizures, motor and cognitive decline, blindness, and premature death. Development of an effective therapy for this disorder will be greatly assisted by the availability of suitable animal models. A mouse PPT-1 gene knockout model has recently been generated. Studies were performed to determine whether the mouse model exhibits ocular features of the human CLN1 disorder. A progressive accumulation of autofluorescent storage material in all layers of the retina was observed in the PPT-1 knockout mice. Accompanying the storage body accumulation was a modest loss of cells with nuclei in the outer and inner nuclear layers. As indicated by electroretinogram (ERG) responses, retinal function was only mildly impaired at 4 months of age but was severely impaired by 8 months, despite only modest changes in retinal morphology. The pupillary light reflex (PLR), on the other hand, was exaggerated in the knockout mice. The apparent anomaly between the ERG and the PLR findings suggests that disease-related PLR changes may be due to changes in extraocular signal processing. The pronounced ocular phenotype in the PPT-1 knockout mice makes these animals a good model for testing therapeutic interventions for treatment of the human CLN1 disorder. © 2006 Wiley-Liss, Inc. [source] Ethanol Consumption Alters Electroretinograms and Depletes Neural Tissues of Docosahexaenoic Acid in Rhesus Monkeys: Nutritional Consequences of a Low n-3 Fatty Acid DietALCOHOLISM, Issue 12 2001Robert J. Pawlosky Background: Alcohol amblyopia is a rare neuropathy characterized by the development of blurred vision and a reduction in visual acuity. Further diagnostic details of this condition have shown abnormalities in the electroretinogram (ERG) that include an increase in implicit times in the a- and b-waves and a depression of b-wave amplitude. Methods: Periodically, the ERGs and the fatty acyl composition of nervous tissue were analyzed from alcohol-consuming rhesus monkeys (Macaca mulatta) (mean consumption 2.6 g kg/day over a 5-year period) and controls that were maintained on a nutritionally sufficient diet that had low, yet adequate, amounts of linoleic acid but very low ,-linolenic acid. Results: Animals consuming alcohol had increased a- and b-wave implicit times and decreased b-wave amplitudes in their electroretinograms compared with those of the dietary control group at 2.5 and 5 years. The fatty acyl composition of brain specimens obtained by surgical biopsy at baseline, 2.5 years, and 5 years demonstrated that docosahexaenoic acid (DHA) had decreased in both groups of animals compared with baseline values. In the brains of the alcohol-treated animals, DHA was even further decreased (2.5 years: ,20%; 5 years: ,33%) compared with the diet controls. In the retinas of the alcohol-consuming animals at 5 years, there was a similar decrease in DHA (-35%) compared with controls. Generally, the n-6 fatty acid, docosapentaenoic acid (DPAn-6) increased in these tissues, apparently compensating for the loss of DHA. Conclusions: A reciprocal change in the DHA/DPAn-6 ratio is known to be associated with abnormal electroretinograms in a number of species. Thus, a marginal intake of n-3 fatty acids in some alcohol abusers may, in part, be responsible for the biochemical changes that underlie the diminished retinal function associated with the visual abnormalities observed in alcohol-amblyopic patients. [source] Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG studyTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2007Claudia Gargini Abstract Retinal degeneration 10 (rd10) mice are a model of autosomal recessive retinitis pigmentosa (RP), identified by Chang et al. in 2002 (Vision Res. 42:517,525). These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE) gene, leading to a rod degeneration that starts around P18. Later, cones are also lost. Because photoreceptor degeneration does not overlap with retinal development, and light responses can be recorded for about a month after birth, rd10 mice mimic typical human RP more closely than the well-known rd1 mutants. The aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the period of maximum photoreceptor degeneration, thus contributing useful data for exploiting this novel model to study RP. We analyzed the morphology and survival of retinal cells in rd10 mice of various ages with quantitative immunocytochemistry and confocal microscopy; we also studied retinal function with the electroretinogram (ERG), recorded between P18 and P30. We found that photoreceptor death (peaking around P25) is accompanied and followed by dendritic retraction in bipolar and horizontal cells, which eventually undergo secondary degeneration. ERG reveals alterations in the physiology of the inner retina as early as P18 (before any obvious morphological change of inner neurons) and yet consistently with a reduced band amplification by bipolar cells. Thus, changes in the rd10 retina are very similar to what was previously found in rd1 mutants. However, an overall slower decay of retinal structure and function predicts that rd10 mice might become excellent models for rescue approaches. J. Comp. Neurol. 500:222,238, 2007. © 2006 Wiley-Liss, Inc. [source] Morphological features of TMPRSS2,ERG gene fusion prostate cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2007J-M Mosquera Abstract The TMPRSS2,ETS fusion prostate cancers comprise 50,70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2,ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2,ERG fusion status using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2,ERG fusion status. Five morphological features were associated with TMPRSS2,ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p -values < 0.05. Only 24% (n = 30/125) of tumours without any of these features displayed the TMPRSS2,ERG fusion. By comparison, 55% (n = 38/69) of cases with one feature (RR = 3.88), 86% (n = 38/44) of cases with two features (RR = 20.06), and 93% (n = 14/15) of cases with three or more features (RR = 44.33) were fusion positive (p < 0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2,ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2,ERG fusion prostate cancer, which may have both prognostic and therapeutic implications. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Comparisons of structural and functional abnormalities in mouse b-wave mutantsTHE JOURNAL OF PHYSIOLOGY, Issue 18 2008Maureen A. McCall In the most simplistic view, the retinal circuit can be divided into vertical excitatory pathways that use glutamate as their neurotransmitter and lateral inhibitory pathways in the outer and inner synaptic layers that modulate excitation via glycine and GABA. Within the vertical excitatory pathways, the visual signal is initiated in the rod, cone or both photoreceptors, depending on the adaptation state of the retina. This signal is transmitted to the rest of the retina through the bipolar cells, which can be subdivided based on: the photoreceptor that provides their input, their dendritic and axonal morphology, and the polarity of their response evoked by a luminance increment, e.g. depolarizing or hyperpolarizing responses. The polarity of this response is controlled by the type of glutamatergic postsynaptic receptor that is expressed on their dendritic terminals. Hyperpolarizing bipolar cells express AMPA/kainate receptors, whereas depolarizing bipolar cells (DBCs) express the metabotropic glutamate receptor 6 (Grm6). The electroretinogram (ERG) is a non-invasive method used to assess overall retinal function. The initiation of the visual signal in the photoreceptors is reflected in the ERG a-wave and the ensuing depolarization of DBCs in the b-wave. When there is failure of signal transmission from photoreceptors to DBCs or signalling within DBCs, the ERG a-wave is present, while the b-wave is absent or significantly reduced. This ERG phenotype has been found in the human population and is referred to as congenital stationary night blindness. Until recently, it had been assumed that the absence of a b-wave was indicative of a lack of signalling through the On pathway, leaving the Off pathway unaffected. Here we review recent findings that demonstrate that many mouse mutants share a no b-wave ERG phenotype but their retinal morphology and RGC responses differ significantly, suggesting very different effects of the underlying mutations on output from the DBCs to the rest of the retinal circuit. [source] Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogramTHE JOURNAL OF PHYSIOLOGY, Issue 10 2008Deb Kumar Mojumder Voltage-gated sodium channels (Nav channels) in retinal neurons are known to contribute to the mammalian flash electroretinogram (ERG) via activity of third-order retinal neurons, i.e. amacrine and ganglion cells. This study investigated the effects of tetrodotoxin (TTX) blockade of Nav channels on the b-wave, an ERG wave that originates mainly from activity of second-order retinal neurons. ERGs were recorded from anaesthetized Brown Norway rats in response to brief full-field flashes presented over a range of stimulus energies, under dark-adapted conditions and in the presence of steady mesopic and photopic backgrounds. Recordings were made before and after intravitreal injection of TTX (,3 ,m) alone, 3,6 weeks after optic nerve transection (ONTx) to induce ganglion cell degeneration, or in combination with an ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 200 ,m) to block light-evoked activity of inner retinal, horizontal and OFF bipolar cells, or with the glutamate agonist N -methyl- d -aspartate (NMDA, 100,200 ,m) to reduce light-evoked inner retinal activity. TTX reduced ERG amplitudes measured at fixed times corresponding to b-wave time to peak. Effects of TTX were seen under all background conditions, but were greatest for mesopic backgrounds. In dark-adapted retina, b-wave amplitudes were reduced only when very low stimulus energies affecting the inner retina, or very high stimulus energies were used. Loss of ganglion cells following ONTx did not affect b-wave amplitudes, and injection of TTX in eyes with ONTx reduced b-wave amplitudes by the same amount for each background condition as occurred when ganglion cells were intact, thereby eliminating a ganglion cell role in the TTX effects. Isolation of cone-driven responses by presenting test flashes after cessation of a rod-saturating conditioning flash indicated that the TTX effects were primarily on cone circuits contributing to the mixed rod,cone ERG. NMDA significantly reduced only the additional effects of TTX on the mixed rod,cone ERG observed under mesopic conditions, implicating inner retinal involvement in those effects. After pharmacological blockade with CNQX, TTX still reduced b-wave amplitudes in cone-isolated ERGs indicating Nav channels in ON cone bipolar cells themselves augment b-wave amplitude and sensitivity. This augmentation was largest under dark-adapted conditions, and decreased with increasing background illumination, indicating effects of background illumination on Nav channel function. These findings indicate that activation of Nav channels in ON cone bipolar cells affects the b-wave of the rat ERG and must be considered when analysing results of ERG studies of retinal function. [source] A novel, spontaneously immortalized, human prostate cancer cell line, Bob, offers a unique model for pre-clinical prostate cancer studies,THE PROSTATE, Issue 14 2009Gerhardt Attard Abstract INTRODUCTION New in vitro models of castration-resistant prostate cancer (CRPC) are urgently required. METHODS Trans-rectal needle biopsies (TRBP) of the prostate were performed for research purposes on progressing CRPC patients who had not received prior treatment to the prostate. Biopsies were immediately digested with collagenase and plated onto collagen-coated flasks with a feeder layer of 3T6 cells and cultured in cytokine-supplemented keratinocyte serum-free medium. RESULTS Biopsies from 25 patients were collected and one of these, following an initial period of crisis, spontaneously immortalized. A series of cell lines called Bob were then established from a clone that survived CD133-selection followed by 4 weeks under adhesion-independent conditions in methylcellulose. Gains and losses previously described in clinical prostate tumors, most notably loss of 8(p) and gain of 8(q), were identified on comparative genomic hybridization and long-term growth in culture, survival in methylcellulose and invasion through matrigel confirmed the malignant phenotype of Bob. Furthermore, Bob expressed high levels of p53 and markers of early differentiation, including K8, prostatic acid phosphatase and prostate stem cell antigen. There was, however, no in vivo growth and ERG and ETV1 were not rearranged. Growth in serum permitted some differentiation. CONCLUSION This is the first spontaneously immortalized prostate cancer cell line to be established from a TRBP of a patient with CRPC. Bob is a novel pre-clinical model for functional studies in CRPC and especially for studying the CRPC "basal" phenotype. Prostate 69: 1507,1520, 2009. © 2009 Wiley-Liss, Inc. [source] TMPRSS2:ERG fusion transcripts in urine from prostate cancer patients correlate with a less favorable prognosisAPMIS, Issue 8 2009KARI ROSTAD Rostad K, Hellwinkel OJC, Haukaas SA, Halvorsen OJ, Øyan AM, Haese A, Budäus L, Albrecht H, Akslen LA, Schlomm T, Kalland K-H. TMPRSS2:ERG fusion transcripts in urine from prostate cancer patients correlate with a less favorable prognosis. APMIS 2009; 117: 575,82. The transcription factor ERG is highly upregulated in the majority of prostate cancers due to chromosomal fusion of the androgen responsive promoter of TMPRSS2 to the ERG reading frame. Our aim was to identify this gene fusion in urine samples from prostate cancer patients prior to radical treatment and to compare fusion status with clinicopathological variables. Urine fractions from 55 patients (with and without prior prostatic massage) were analyzed for the presence of TMPRSS2:ERG isoforms using real-time qPCR. Sixty-nine percent of urine samples following prostatic massage were positive for TMPRSS2:ERG isoforms a or b, five out of which were positive for both, vs 24% of samples obtained without prior massage. Isoform a seems to be most prevalent and some patients may be positive for more than one fusion variant, reflecting the multifocality of prostate cancer. Prostatic massage prior to sampling, analysis of pelleted urine material and detection of cDNA provided the highest sensitivity. Positive statistical correlations were identified between TMPRSS2:ERG fusion and high s-PSA, pathological stage and Gleason score. Our findings contribute to the increasing elucidation of the role of TMPRSS2:ERG in the development of prostate cancer. [source] The Wilcoxon Signed Rank Test for Paired Comparisons of Clustered DataBIOMETRICS, Issue 1 2006Bernard Rosner Summary The Wilcoxon signed rank test is a frequently used nonparametric test for paired data (e.g., consisting of pre- and posttreatment measurements) based on independent units of analysis. This test cannot be used for paired comparisons arising from clustered data (e.g., if paired comparisons are available for each of two eyes of an individual). To incorporate clustering, a generalization of the randomization test formulation for the signed rank test is proposed, where the unit of randomization is at the cluster level (e.g., person), while the individual paired units of analysis are at the subunit within cluster level (e.g., eye within person). An adjusted variance estimate of the signed rank test statistic is then derived, which can be used for either balanced (same number of subunits per cluster) or unbalanced (different number of subunits per cluster) data, with an exchangeable correlation structure, with or without tied values. The resulting test statistic is shown to be asymptotically normal as the number of clusters becomes large, if the cluster size is bounded. Simulation studies are performed based on simulating correlated ranked data from a signed log-normal distribution. These studies indicate appropriate type I error for data sets with ,20 clusters and a superior power profile compared with either the ordinary signed rank test based on the average cluster difference score or the multivariate signed rank test of Puri and Sen (1971, Nonparametric Methods in Multivariate Analysis, New York: John Wiley). Finally, the methods are illustrated with two data sets, (i) an ophthalmologic data set involving a comparison of electroretinogram (ERG) data in retinitis pigmentosa (RP) patients before and after undergoing an experimental surgical procedure, and (ii) a nutritional data set based on a randomized prospective study of nutritional supplements in RP patients where vitamin E intake outside of study capsules is compared before and after randomization to monitor compliance with nutritional protocols. [source] 4341: Are visual evoked potentials and pattern ERG useful in neuro-ophthalmology?ACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To describe the roles of VEP and PERG in clinical neuroophthalmology. Methods Case based examples. Results Objective visual system testing with electrophysiology allows the distinction between optic nerve and macular dysfunction, often difficult in clinical practice. Examples will be shown of the types of VEP abnormality that can occur in different disorders of optic nerve function. PERG should also be performed in the patient with visual symptoms; if the PERG suggests macular dysfunction, full-field ERG is indicated in order to determine whether that macular dysfunction is part of a generalised retinal process or is dysfunction localised to the macula. Electrophysiology further allows the diagnosis of non-organic visual loss and the quantification of visual system dysfunction. Conclusion The objective functional assessment with electrophysiology is an important part of the diagnostic armamentarium available to neuroophthalmologists. [source] 4224: The role of electrophysiologyACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To describe the roles of electrophysiology in patients with medically unexplained visual loss Methods Standardised full-field and pattern ERGs and VEPs; additional pattern appearance VEPs to quantify visual system resolution when necessary in patients with suspected non-organic visual loss. Results Selected cases will be used to illustrate the roles of electrophysiology. A diagnosis of non-organic visual loss is confirmed by the demonstration of normal visual system function in the presence of symptoms that suggest otherwise. Patients with optic nerve disease may have a normal fundus appearance, and not all macular dysfunction is associated with an abnormal appearance of the macula; both pattern VEP and pattern ERG are needed in such cases. Further, there are many patients with retinal disease where the fundus appearance may be normal but ERGs are abnormal. Conclusion Objective functional assessment with electrophysiology is indispensable to the diagnosis and management of patients with medically unexplained visual loss. [source] 2466: Blue cone nonochromacy gene mutation in Asia: phenotype variabilityACTA OPHTHALMOLOGICA, Issue 2010P BITOUN Purpose A far East asian family with 4 affected maternal cousin males with congenital nystagmus, low vision and dyschromatopsia was investigated for a genetic cause after informed consent. Blue cone monochromacy is a rare form of X-linked visual handicap with dyschromatopsia. Methods Family members had ophthalmologic examination including visual acuity, fundoscopy , slit lamp, biomicroscopy,colour vision testing and ERG and VEP recordings.DNA analysis of the composition of the cone ospin gene cluster was performed by PCR and PCR/RFLP as well as direct sequencing of LWS opsin gene. Results A novel nonsense Mutation in the single Long wave sensitive opsin gene was identified in all affected males and carrier females. The variability of the phenotype as well as the added role of parental myopia transmission in the phenotype will be discussed. Conclusion This is the first reported molecular diagnosis of blue cone monochromacy in the Asian population. The compound effect of dominantly inherited myopia offers insight of the effect of the added mutational load in these patients. [source] 2245: Electrodiagnosis in inherited retinal diseaseACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To describe the roles of electrophysiology in the diagnosis and counselling of patients with inherited retinal disease. Methods Electrophysiological testing performed to incorporate and extend the recommendations of the International Society for Clinical Electrophysiology of Vision. Results Using a case-based presentation, it will be shown that electrophysiological testing can objectively assess the function of the different cell types and layers within the retina of the patient with inherited retinal dysfunction, which enables accurate diagnosis and counselling when placed in clinical context. The roles of pattern and multi-focal ERG in the assessment of macular function will be discussed. The electrophysiological findings will be discussed in relation to imaging studies when appropriate. It will shown that distinctive electrophysiological findings can direct appropriate and therefore cost-effective mutational screening in patients with atypical fundus changes. Conclusion Electrophysiological testing is fundamental to the successful management of patients with inherited disorders of retinal function. [source] 4122: Exploring new strategies to record and analyse clinical electroretinogramsACTA OPHTHALMOLOGICA, Issue 2010P LACHAPELLE Purpose Investigate if the combination of time-frequency domain analysis and ERG dipole rotation reveals hidden features of the normal ERG that could be instrumental in the interpretation of nearly extinguished ERG responses. Methods Analyses were conducted on photopic ERGs (Photopic Hills: PH) obtained from normal subjects (n=75) and patients (n=65) affected with various retinopathies. A Discrete Wavelet Transform (DWT) was done on each ERGs and key descriptors (Holder exponent and wavelet coefficient maxima) were calculated. Dipole rotation was obtained by combining 11 gaze positions (0, 8, 16, 24, 32 and 40 degrees nasal or temporal to center) with 4 electrode locations [corneal (CE), lower lid (LL), external (EC) and internal canthi (IC)]. Results The Holder exponent follows a parabola, while some of the local wavelet maxima seem to follow a PH-like like distribution (b-wave and OPs) or a logistic growth function (a-wave). In still recordable pathological ERGs, the wavelet maxima matched that found in normal ERGs evoked at low stimulus intensities while in nearly extinguished ERGs (<10% of normal) the wavelet coefficients were significantly lower. Irrespective of the direction of gaze, there was little variation in DTL ERGs. EC ERGs were the only ones to reverse in polarity (seen 5 degrees nasal to fixation in nasal to temporal shift). Conclusion The parameters obtained with the DWT offers useful and reproducible tools to help identify subtle features of residual ERGs and therefore should allow for a more accurate quantification of low-voltage ERGs responses. Finally, our results suggest that varying the gaze and electrode positions would represent a valuable addition to the recording of clinical ERGs. Funded by NSERC. [source] 4125: Phenotypic variability in association with mutation in RDS/peripherinACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To report the clinical and electrophysiological findings associated with autosomal dominant maculopathy caused by mutations in Rds/peripherin. Methods Fifty three individuals with autosomal dominant macular dystrophy and a confirmed molecular diagnosis of Rds/peripherin mutation were ascertained between January 2002 and December 2008. International-standard pattern and full-field electroretinograms (PERG; ERG) were performed in 38 cases. Electro-oculograms (EOG) were performed in 25 cases. Results Fourteen different mutations were identified in the Rds/peripherin gene; 4 of which were novel. Twenty four (45%) patients had the common p.Arg172 Trp allele. The mean age at the time of first symptoms and at diagnosis was 35.0+/- 2.4 and 47.1 +/- 1.5 years old [SEM] respectively. Mean LogMAR visual acuity at presentation was 0.5+/- 0.08 [SEM]. Fundus phenotypes included central atrophy (19 cases), pattern dystrophy (10 cases), maculopathy with flecks (5 cases), and adult vitellifom dystrophy (4 cases). Pattern ERG P50 reduction was seen in 75 of 76 eyes; the majority having undetectable or residual responses, including some cases with preserved visual acuity. ERG ranged from normal to severe reduction in both cone and rod driven responses and were not predictable either from the fundus appearance or from the specific mutation in Rds/peripherin; on addition, marked intra-familial variation could be noted. Conclusion Mutations in the Rds/peripherin gene result in a wide variety of fundus and functional phenotypes. The same mutation can result in profoundly different phenotypes, even within family members. [source] 2126: Retinal and cortical functions in adult mice lacking cannabinoid receptorsACTA OPHTHALMOLOGICA, Issue 2010C CASANOVA Purpose Cannabinoid receptor type 1 (CB1R) has been localized in the adult retina of rodents. It is expressed in cones, horizontal, bipolar, some amacrine and ganglion cells. The expression of the cannabinoid receptor type 2 (CB2R) mRNA in the retina of adult rats was also reported. The goal of the present study was to investigate the functional roles of CB1R and CB2R in the retina by comparing retinal electrophysiological responses and cortical optical signals in normal and genetically modified mice. Methods Experiments were conducted on four different groups of C57BL/6 mice: CB1R wild type (WT), CB1R knockout (KO), CB2R WT and KO. Scotopic electroretinograms (ERG) luminance-response functions and photopic ERGs were recorded. In a subset of CB1 groups, intrinsic signals acquired by optical brain imaging were used to determine spatial frequency, contrast sensitivity and retinotopic maps in the visual cortex. Results The CB1R KO retina showed a stronger photopic response. No differences were observed for scotopic responses. For the CB2R groups, the scotopic b-wave response was stronger in the KO mice. No differences could be seen between visual cortices maps with respect to SF and contrast sensitivity. Retinotopic maps differed only along the azimuth. Significant differences were observed between hemodynamic response functions. Conclusion These results indicate that CB receptors can play a regulatory effect on the neurovascular coupling at the retinal and cortical levels and on the functional organization of the mice visual cortex along the azimuth Axis.(NSERC) [source] Electrophysiological evaluation and visual outcome in patients with central retinal vein occlusion, primary open-angle glaucoma and neovascular glaucomaACTA OPHTHALMOLOGICA, Issue 1 2010Elisabeth Wittström Abstract. Purpose:, To evaluate patients with central retinal vein occlusion (CRVO) and neovascular glaucoma (NVG) using electrophysiology in order to gain better understanding of visual outcome and risk factors, such as previously diagnosed primary open-angle glaucoma (POAG). Methods:, Eighty-three patients (83 eyes) initially presenting with CRVO and examined with full-field electroretinography (ERG) within 3 months of the thrombotic event were analysed retrospectively regarding treatment, risk factors and visual outcome. In addition, 30 patients initially presenting with NVG caused by CRVO were also investigated regarding risk factors using electrophysiology in order to determine the cause of their visual impairment. Results:, Nineteen (23%) of the 83 patients initially presenting with CRVO had been diagnosed previously with POAG. Ninety-five per cent (18/19) of all the patients with previously diagnosed glaucoma developed ischaemic CRVO. Thirty-four per cent of the patients initially presenting with CRVO (28/83) developed NVG. Sixty-eight per cent (13/19) of the patients with previous glaucoma developed NVG, compared to 23% (15/64) of the patients without previous POAG. In the patients who initially presented with NVG, full-field ERG demonstrated a remaining retinal function of both cones and rods, indicating that the main cause of visual impairment is ischaemia of the ganglion cell layer. Conclusion:, Glaucoma is a significant risk factor for developing ischaemic CRVO and subsequent NVG. The presence of POAG in CRVO worsens visual outcome. NVG is associated with preserved photoreceptor function, thus indicating ischaemia of the ganglion cell layer as the primary cause of visual impairment. This emphasizes the importance of prompt treatment of ischaemia and elevated intraocular pressure in these patients. [source] Antagonists of ionotropic ,-aminobutyric acid receptors impair the NiCl2 -mediated stimulation of the electroretinogram b-wave amplitude from the isolated superfused vertebrate retinaACTA OPHTHALMOLOGICA, Issue 8 2009Siarhei A Siapich Abstract. Purpose:, NiCl2 (15 ,M) stimulates the electroretinogram (ERG) b-wave amplitude of vertebrate retina up to 1.5-fold through its blocking of E/R-type voltage-gated Ca2+ channels. Assuming that such an increase is mediated by blocking the release of the inhibitory neurotransmitter ,-aminobutyric acid (GABA) via ionotropic GABA receptors, we tested the effect of both GABA itself and GABA-receptor antagonists such as (,)bicuculline (1.51-fold increase) and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA; 1.46-fold increase) on the b-wave amplitude. Methods:, Recording of the transretinal potentials from the isolated bovine retina. Results:, GABA (100 ,M) reduced the b-wave amplitude only when NiCl2 (15 ,M) was applied first. Each antagonist applied on its own stimulated the b-wave amplitude only partially: subsequent NiCl2 superfusion caused a small but additional increase, leading to a 1.69- and a 1.88-fold total increase of the amplitude by Ni2+ plus (,)bicuculline or Ni2+ plus TPMPA, respectively. Only the application of both antagonists in combination, before superfusing low NiCl2 (15 ,M), completely prevented subsequent stimulation by NiCl2 with a similar 1.90-fold total increase of b-wave amplitude. Those retina segments that did not respond to NiCl2 could not be stimulated by (,)bicuculline and vice versa. Conclusion:, The stimulatory effect of NiCl2 on the ERG b-wave amplitude is mainly, but not only, mediated by a NiCl2 -sensitive, Cav2.3-triggered GABA release acting through ionotropic GABA-A and GABA-C receptors. [source] The effects of sub-conjunctival EPO administration on ERG and on the peripheral blood haematocrit in animal model (rabbit)ACTA OPHTHALMOLOGICA, Issue 2009E DELGADO Purpose To assess the effects of subconjunctival EPO administration on retinal eletrophysiology and on the peripheral blood haematocrit. Methods New Zealand White rabbits (n=6) received 100 UI of EPO through the subconjuntival route. Blood for Complete Blood Count (CBC) was collected on day 0, on day 7 and on day 14 of the experimental protocol. Furthermore electroretinograms were performed on day 0 and on day 30 of the experiments. Results Regarding CBC changes, the haematocrit values changed from 35,42±2,7% on day 0 to 34,32±4,3% (p=0,390) on day 7 and to 34,45±4,4% on day 14 (p=0,931), showing no significant changes. Concerning the red blood cells (RBC x10000/µL) count, the values evolved from 6,02±0,48 on day 0 to 5,65±0,67 (p=0,074) on day 7 and to 5,67±0,74 (p=0,948) on day 14, showing no significant alterations. On the contrary, on what regards the electroretinograms, although there were no significant changes on a-wave amplitudes, which evolved from 13,94±1,7 µV on day 0 to 13,67±0,8 µV on day 30 (p=0,844) and no significant differences on N1-P1 amplitudes which changed from 46,60±4,5µV to 55,48±10,5 µV (p=0,438), there was a remarkable increase on b-wave amplitude of 49%, changing from 46,60±7,43 µV to 94,97±13,36 µV (p=0,031). Conclusion On what concerns CBC profiles, subconjuntival EPO administration did not cause any sinificant changes on haematocrit or RBC values. Regarding electrorretinography, there were no significant changes on a-wave or N1-P1 amplitudes, but there was a marked increase in the b-wave amplitude which tests for photoreceptor functionality, which might indicate a protective action against apoptosis of retinal photoreceptors even in physiological conditions. [source] Tolerance and safety of ocular use of recombinant human erythropoietin (rhEPO).ACTA OPHTHALMOLOGICA, Issue 2009Neuroprotective effects in ocular hypertension/glaucoma Purpose The purpose of this study was to evaluate the long-term effects of monthly intravitreal injections of rhEPO in a rabbit model. Methods Sixteen New Zealand rabbits were divided into 4 groups: control (no injection), saline injection, or rhEPO injections of 500 U and 1000 U (N=4 per group). The right eye of each animal was injected monthly over a period of 7 months. Fundus examination and electroretinography (ERG) were performed at 1 day prior, and 1 week, 1 month, and 6 months after the initial injection. After the final ERG, animals underwent fluorescein angiography and sacrifice one week later. Scotopic and photopic ERG amplitude and implicit times were analyzed by calculating a ratio between the right and the left eyes. Angiograms were graded for the presence of neovascularization or leakage. Statistical analysis was carried out using two-way ANOVA. Results Fifteen animals were used for this experiment (1 developed a traumatic cataract and was excluded). Between all groups and time points, there were no statistically significant differences in the computed right eye:left eye ratios for the scotopic or photopic ERG components (p>0.05). No evidence of neovascularization or fluorescein leakage was seen on angiography. There were no visible differences in retinal architecture or thickness in the rhEPO groups when compared to uninjected controls. Conclusion Monthly 0.1 ml intravitreal injections of rhEPO at a dose of up to 1000 U over 7 months is well-tolerated and does not cause adverse effects on retinal function, architecture, or vasculature in a rabbit model. A review of published data on rhEPO and Glaucoma will also be presented. [source] Gene therapy mediates cone rescue and rejuvenation in the R91W mutant form of Rpe65-deficiency miceACTA OPHTHALMOLOGICA, Issue 2009Y ARSENIJEVIC Purpose Given the advances of gene therapy studies to cure RPE65-derived Leber Congenital Amaurosis (LCA) (clinical trials phase I), it is of prime importance to examine how cones can be rescued in different mutant contexts. Consequently, we evaluated the effect on retinal activity and cone survival of lentivirus-mediated gene therapy in the R91W knock-in mouse model expressing the mutant Rpe65R91W gene. Methods An HIV-1-derived lentiviral vector (LV) expressing either the GFP or the mouse Rpe65 cDNA under the control of a 0.8 kb fragment of the human Rpe65 promoter (R0.8) was produced. LV-R0.8-RPE65 or GFP was injected into 5-days-old (P5) or 1 month-old R91W mice. Functional and morphological retinal rescues were investigated at 4 months of age. Results Increased light sensitivity was detected by ERG and pupillary light responses in animals injected with LV-R0.8-RPE65 at both P5 and 1 month compared to controls. Histological analysis showed improved expression of cone markers and cone outersegment morphology. Furthermore, the density of cones in the region of RPE65 delivery after treatment at P5 reached the wild type level. However, before injection at 1 month of age, only a fraction of the cones (40% of the number found in WT animals) in the Rpe65R91W/R91W mice expressed cone transducin, this fraction increased to 64% after treatment. Moreover, these cones appeared normal. Conclusion We show that lentivirus-mediated Rpe65 gene transfer is very efficacious in early treatments and still efficient during the course of cone degeneration. Moreover, the treatment at 1 month shows a rejuvenation process of the diseased cones. Thus patient suffering from R91W mutation might benefit from a prolonged therapeutic window. [source] Importance of electroretinogram in bull's eye maculopathyACTA OPHTHALMOLOGICA, Issue 2009R HALFELD FURTADO DE MENDONCA Purpose To describe the retinographic, electroretinographic and ultra-structural alteration in a interesting family case of bull's eye maculopathy. Methods A 14-year-old boy, his brother a 12-year-old boy and his sister a 10-year-old girl with visual loss, underwent complete ophthalmological exams, including retinography, electroretinography (ERG) and ultrastructural study by electron microscopy of the skeletal muscle, at the Clinical Hospital of the University of São Paulo. Results All three children presented optic nerve pallor, arteriolar thinning and bull's eye maculopathy. The scotopic responses were absent or with low amplitude contrasting with normal flicker responses. Electron microscopy study detected the curvilinear bodies typical from Neuronal Ceroid Lipofucinosis (NCL). Conclusion The initial diagnose of those children was cone-rod dystrophy. Diagnosis of NCL was established by normal ERG flicker and findings of characteristic electron microscopic curvilinear bodies. The electrophysiologic testing are very important in the early diagnosis of NCL. [source] Studying electrophysiological characteristics in children with congenital sensory nystagmus- case presentationsACTA OPHTHALMOLOGICA, Issue 2009J BRECELJ Purpose In classification of sensory congenital nystagmus (CN) is important to recognize the underlying retinal or visual pathway dysfunction. The aim was to distinguish ERGs and VEPs charcteristics which may identify among variety of disorders associated with sensory CN. Methods In infants and small children that were ophthalmologically classified as sensory CN were ERGs and VEPs recorded simultaneously in the same session. ERGs were detected without dilated pupils and with skin electrodes. Under darkened laboratory conditions were ERGs recorded to white (cone/rod mediated response) and dim blue (rod mediated response) flash and under lighten room were ERGs recorded to white, red and 30 Hz flicker flash (cone mediated responses). VEPs were recorded from three occipital electrodes to flash and onset stimulation. Results Cases with abnormal ERGs showed: in Leber's congenital amaurosis were undetectable both rod and cone mediated responses from early infancy; in cone-rod retinal dystrophy abnormal cone and rod mediated responses progressed in time; in achromatopsia abnormal cone mediated responses did not progress in time; in congenital stationary night blindness a negative ERG did not progress in time. Cases with abnormal VEPs showed: in ocular albinism VEP contralateral asymmetry; in achiasmia VEP ipsilateral asymmetry; in severe optic nerve hypoplasia flash VEP was non-recordable, while in moderate optic nerve hypoplasia flash and pattern onset VEP findings might not correlate with clinic findings. Conclusion Sensory CN is associated with a variety of disorders affecting the retina, optic nerve, chiasm and electrophysiology may characterize retinal or postretinal pathway dysfunction and therefore help in early diagnosis. [source] | ||||||||||||||||||||||||||||