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Congenital Stationary Night Blindness (congenital + stationary_night_blindness)
Selected AbstractsMathematical analysis of the cone ERG photopic hill: Clinical applicationsACTA OPHTHALMOLOGICA, Issue 2007P LACHAPELLE Purpose: With brighter stimuli, the photopic ERG b-wave increases to a maximal value and then decreases to a plateau, a feature known as the Photopic Hill (PH). Recently, a mathematical model combining a Gaussian (GF) and a Logistic Growth (LGF) functions was developed to fit the PH (Hamilton et al., Vision Research, in press). We examined if this equation could help us sort out selected retinopathies. Methods: We compared PHs (background: 30 cd.m-2; intensities: -0.8 to 2.84 log cd.sec.m-2) obtained from normals (N=40) and patients (N=20) affected with Congenital Stationary Night Blindness (CSNB), Congenital Postreceptoral Cone Pathway Anomaly (CPCPA) and Retinitis Pigmentosa (RP) with the GL ratio [GL= Gb / (Gb+Vbmax)] were Gb and Vbmax represent the amplitude of the Gaussian and logistic (Vbmax) functions respectively. Results: The normal GL ratio is 0.60 ± 0.08 (mean ± 1SD) compared to ,1.0 in CSNB (almost pure GF) and 0.32±0.08 in CPCP [reduced GF (p<.05) and normal LF (p>.05)] patients. Six of the 8 RP patients had a GL ratio above 0.5 (mean GL= 0.70 ± 0.19) and 2 below (0.28 and 0.41). Of interest, while in some retinopathies, a decline in Gb and Vbmax occurred with disease progression (longitudinal and transversal comparisons), it did not always modify the GL ratio. Conclusions: Human PH can be dissected into two distinct and concomitant phenomena each represented by its own equation. Altghough the retinal origin of the GF and LGF awaits to be confirmed, use of this mathematical approach appears to add valuable information that will further refine the diagnosis of retinal disorders affecting the photopic (cone) pathway. Supported by CIHR and Réseau Vision. [source] p.Gln200Glu, a putative constitutively active mutant of rod ,-transducin (GNAT1) in autosomal dominant congenital stationary night blindness,,HUMAN MUTATION, Issue 7 2007Viktoria Szabo Abstract Congenital stationary night blindness (CSNB) is a non-progressive Mendelian condition resulting from a functional defect in rod photoreceptors. A small number of unique missense mutations in the genes encoding various members of the rod phototransduction cascade, e.g. rhodopsin (RHO), cGMP phosphodiesterase ,-subunit (PDE6B), and transducin ,-subunit (GNAT1) have been reported to cause autosomal dominant (ad) CSNB. While the RHO and PDE6B mutations result in constitutively active proteins, the only known adCSNB-associa-ted GNAT1 change (p.Gly38Asp) produces an ,-transducin that is unable to activate its downstream effector molecule in vitro. In a multigeneration Danish family with adCSNB, we identified a novel heterozygous C to G transversion (c.598C>G) in exon 6 of GNAT1 that should result in a p.Gln200Glu substitution in the evolutionarily highly conserved Switch 2 region of ,-transducin, a domain that has an important role in binding and hydrolyzing GTP. Computer modeling based on the known crystal structure of transducin suggests that the p.Gln200Glu mutant exhibits impaired GTPase activity, and thereby leads to constitutive activation of phototransduction. This assumption is in line with our results of trypsin protection assays as well as previously published biochemical data on mutants of this glutamine in the GTPase active site of ,-transducin following in vitro expression, and observations that inappropriately activating mutants of various members of the rod phototransduction cascade represent one of the major molecular causes of adCSNB. © 2007 Wiley-Liss, Inc. [source] Canine inhertited retinal degenerations: update on molecular genetic research and its clinical applicationJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2002C-T. Lin Inherited retinal degenerations in the dog include generalized progressive retinal atrophy, retinal pigment epithelial dystrophy, congenital stationary night blindness and day blindness (hemeralopia). The clinical phenotype and pathology of these diseases closely resemble some types of human inherited retinal degeneration, in particular retinitis pigmentosa, one of the most common inherited causes of blindness in man. Molecular genetic investigations aim to identify the genetic mutations underlying the canine inherited retinal degenerations. Two major research strategies, candidate gene analysis and linkage analysis, have been used. To date, candidate gene analysis has definitively identified the genetic mutations underlying nine inherited retinal degenerations, each in a different breed of dog, and linkage studies have identified genetic markers for a further retinal degeneration which is found in at least six different breeds. This review outlines the research strategy behind candidate gene and linkage studies and summarises recent results in the search for genetic causes of canine inherited retinal degenerations. The aim is to increase awareness of this rapidly changing field and to show how the research can be used to develop genetic tests for these diseases and thereby reduce the incidence of inherited eye disease in dogs. [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] TRPM1: The endpoint of the mGluR6 signal transduction cascade in retinal ON-bipolar cellsBIOESSAYS, Issue 7 2010Catherine W. Morgans Abstract For almost 30 years the ion channel that initiates the ON visual pathway in vertebrate vision has remained elusive. Recent findings now indicate that the pathway, which begins with unbinding of glutamate from the metabotropic glutamate receptor 6 (mGluR6), ends with the opening of the transient receptor potential (TRP)M1 cation channel. As a component of the mGluR6 signal transduction pathway, mutations in TRPM1 would be expected to cause congenital stationary night blindness (CSNB), and several such mutations have already been identified in CSNB families. Furthermore, expression of TRPM1 in both the retina and skin raises the possibility that a genetic link exists between certain types of visual and skin disorders. [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] The key role of electrophysiology in the diagnosis of visually impaired childrenACTA OPHTHALMOLOGICA, Issue 6 2006Maria Van Genderen Abstract. Purpose:, To describe the outcome of specialized electrophysiology in visually impaired children. Methods:, We carried out a retrospective evaluation of 340 electrophysiological examinations performed in 298 children over a 3-year period (2001,2003), with regard to demographic data, referral pattern, degree of compliance, and diagnostic results. Electrophysiology was performed without sedation or anaesthesia. In electroretinograms, DTL electrodes were used in combination with online selection of responses. Visual evoked potentials testing was performed with seven active occipital electrodes. Results:, The mean age of the children was 7 ± 5 years; 72 (24%) of the children were mentally as well as visually impaired. Main reasons for referral were suspected posterior segment disease, abnormal visual development, unexplained low vision, high myopia, and suspected albinism. Compliance was good in 302/340 (88%), partial in 24/340 (7%), and absent in 14/340 (4%) of the examinations. Of the 326 successful procedures, 215 (66%) showed abnormal results. Tapetoretinal dystrophy (22%), opticopathy (16%), congenital stationary night blindness (13%), and cone dystrophy (11%) were the most frequently established diagnoses. Albinism was confirmed in 14 of 24 suspected patients; additionally, unsuspected misrouting was found in six. In 26 (9%) of the patients, a previously established diagnosis was changed. Conclusions:, In a specialized setting, electrophysiological examinations can be performed successfully in visually impaired children. The results are essential for the final ophthalmological diagnosis and have important consequences for rehabilitation. [source] | |||||||||||||