The Experts below are selected from a list of 2250 Experts worldwide ranked by ideXlab platform
Beerend H J Winkelman - One of the best experts on this subject based on the ideXlab platform.
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Nystagmus in patients with Congenital stationary night blindness csnb originates from synchronously firing retinal ganglion cells
PLOS Biology, 2019Co-Authors: Beerend H J Winkelman, Majbritt Holzel, Coen Joling, Kathryn H Fransen, Gobinda Pangeni, Sander Kamermans, Hiraki Sakuta, Marcus H C Howlett, Masaharu NodaAbstract:Congenital Nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here, we investigated whether Nystagmus associated with Congenital stationary night blindness (CSNB) results from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lacked functional nyctalopin protein (NYX, nyx) in ON bipolar cells (BCs) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4–7 Hz. nob ON direction-selective ganglion cells (DSGCs), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GCs) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light when contrast was present. Retinal pharmacological and genetic manipulations that blocked nob GC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced the oscillation frequency of nob GCs also reduced the oscillation frequency of their eye movements. We conclude that, in nob mice, synchronized oscillations of retinal GCs, most likely the ON-DCGCs, cause Nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of Congenital Nystagmus, paving the way for development of therapeutic strategies.
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Nystagmus in patients with Congenital stationary night blindness csnb originates from synchronously firing direction selective retinal ganglion cells
bioRxiv, 2019Co-Authors: Beerend H J Winkelman, Marcus Howlett, Majbritt Holzel, Coen Joling, Kathryn H Fransen, Gobinda Pangeni, Sander Kamermans, Hiraki Sakuta, Masaharu Noda, H J SimonszAbstract:Abstract Congenital Nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here we investigated whether Nystagmus associated with Congenital stationary nightblindness (CSNB) can result from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lack functional nyctalopin protein (NYX, nyx) in ON bipolar cells (ON-BC) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4-7Hz. nob ON direction selective ganglion cells (ON-DSGC), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GC) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light. Retinal pharmacological manipulations that blocked nob ON-DSGC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced oscillation frequency of nob ON-DSGCs also reduced oscillation frequency of their eye movements. We conclude that, in nob mice, oscillations of retinal ON-DSGCs cause Nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of Congenital Nystagmus paving the way for development of therapeutic strategies.
Rebecca J. Mclean - One of the best experts on this subject based on the ideXlab platform.
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Congenital Nystagmus randomized controlled double masked trial of memantine gabapentin
Annals of Neurology, 2007Co-Authors: Rebecca J. Mclean, Frank A Proudlock, Shery Thomas, Chris Degg, Irene GottlobAbstract:Objective Nystagmus consists of involuntary to and fro movements of the eyes. Although studies have shown that memantine and gabapentin can reduce acquired Nystagmus, no drug treatment has been systematically investigated in Congenital Nystagmus. Methods We performed a randomized, double-masked, placebo-controlled study investigating the effects of memantine and gabapentin on Congenital Nystagmus over a period of 56 days. The primary outcome measure was logarithmic minimum angle of resolution (logMAR) visual acuity; the secondary outcome measures were Nystagmus intensity and foveation, subjective questionnaires about visual function (VF-14) and social function. Analyses were by intention to treat. Results Forty-eight patients were included in the study. One patient in the placebo group dropped out. Patients were randomized into either a memantine group (n = 16), gabapentin group (n = 16), or placebo group (n = 15). Mean visual acuity improvements showed a significant effect between treatment groups (F = 6.2; p = 0.004, analysis of variance) with improvement in both memantine and gabapentin groups. Participants with afferent visual defects showed poorer improvements in visual acuity to medication than those with apparently normal visual systems. However, eye movement recordings showed that both Nystagmus forms improved in Nystagmus intensity (F = 7.7; p = 0.001) and foveation (F = 8.7; p = 0.0007). Participants subjectively reported an improvement in vision after memantine and gabapentin treatment more often than in the placebo group (p = 0.03). However, there were no significant differences between the treatment groups with visual function (VF-14) or social function questionnaires because all groups reported improvements. Interpretation Our findings show that pharmacological agents such as memantine and gabapentin can improve visual acuity, reduce Nystagmus intensity, and improve foveation in Congenital Nystagmus. Ann Neurol 2007
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mutations in frmd7 a newly identified member of the ferm family cause x linked idiopathic Congenital Nystagmus
Nature Genetics, 2006Co-Authors: Patrick S Tarpey, N Sarvananthan, Shery Thomas, Uma Mallya, Steven Lisgo, Christopher J Talbot, E O Roberts, M Awan, M Surendran, Rebecca J. McleanAbstract:Idiopathic Congenital Nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic Congenital Nystagmus. Screening of 42 singleton cases of idiopathic Congenital Nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.
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the effects of gabapentin and memantine in acquired and Congenital Nystagmus a retrospective study
British Journal of Ophthalmology, 2006Co-Authors: Thomas Shery, Rebecca J. Mclean, Frank A Proudlock, N Sarvananthan, Irene GottlobAbstract:Background: Pharmacological treatment has been successful in some forms of acquired neurological Nystagmus. However, drugs are not known to be effective in idiopathic infantile Nystagmus or Nystagmus associated with ocular diseases. Methods: The authors retrospectively analysed Snellen visual acuity (VA), subjective visual function, and eye movement recordings of 23 patients with Nystagmus (13 secondary to multiple sclerosis, three associated with other neurological diseases, two idiopathic infantile, and five with associated ocular diseases) treated with gabapentin or memantine. Results: With gabapentin, 10 of 13 patients with Nystagmus secondary to multiple sclerosis (MS) showed some improvement. Memantine improved the VA in all three patients with MS who did not improve on gabapentin. There was no change of Nystagmus in other neurological disorders. Patients with Congenital Nystagmus showed reduction of Nystagmus and their VA changes depended on the ocular pathology. Conclusion: Gabapentin and memantine may be effective in acquired Nystagmus secondary to MS. To the authors’ knowledge this is the first series of patients showing that gabapentin is effective in improving Nystagmus in Congenital Nystagmus/Nystagmus associated with ocular pathology. Memantine may be useful as an alternative drug in treating patients with Nystagmus.
Masaharu Noda - One of the best experts on this subject based on the ideXlab platform.
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Nystagmus in patients with Congenital stationary night blindness csnb originates from synchronously firing retinal ganglion cells
PLOS Biology, 2019Co-Authors: Beerend H J Winkelman, Majbritt Holzel, Coen Joling, Kathryn H Fransen, Gobinda Pangeni, Sander Kamermans, Hiraki Sakuta, Marcus H C Howlett, Masaharu NodaAbstract:Congenital Nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here, we investigated whether Nystagmus associated with Congenital stationary night blindness (CSNB) results from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lacked functional nyctalopin protein (NYX, nyx) in ON bipolar cells (BCs) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4–7 Hz. nob ON direction-selective ganglion cells (DSGCs), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GCs) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light when contrast was present. Retinal pharmacological and genetic manipulations that blocked nob GC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced the oscillation frequency of nob GCs also reduced the oscillation frequency of their eye movements. We conclude that, in nob mice, synchronized oscillations of retinal GCs, most likely the ON-DCGCs, cause Nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of Congenital Nystagmus, paving the way for development of therapeutic strategies.
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Nystagmus in patients with Congenital stationary night blindness csnb originates from synchronously firing direction selective retinal ganglion cells
bioRxiv, 2019Co-Authors: Beerend H J Winkelman, Marcus Howlett, Majbritt Holzel, Coen Joling, Kathryn H Fransen, Gobinda Pangeni, Sander Kamermans, Hiraki Sakuta, Masaharu Noda, H J SimonszAbstract:Abstract Congenital Nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here we investigated whether Nystagmus associated with Congenital stationary nightblindness (CSNB) can result from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lack functional nyctalopin protein (NYX, nyx) in ON bipolar cells (ON-BC) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4-7Hz. nob ON direction selective ganglion cells (ON-DSGC), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GC) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light. Retinal pharmacological manipulations that blocked nob ON-DSGC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced oscillation frequency of nob ON-DSGCs also reduced oscillation frequency of their eye movements. We conclude that, in nob mice, oscillations of retinal ON-DSGCs cause Nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of Congenital Nystagmus paving the way for development of therapeutic strategies.
Jan Müller - One of the best experts on this subject based on the ideXlab platform.
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Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity
Neuron, 2015Co-Authors: Keisuke Yonehara, Michele Fiscella, Antonia Drinnenberg, Federico Esposti, Jacek Krol, Felix Franke, Brigitte Gross Scherf, Stuart Trenholm, Akos Kusnyerik, Jan MüllerAbstract:Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human Congenital Nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.
Patrick S Tarpey - One of the best experts on this subject based on the ideXlab platform.
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cask mutations are frequent in males and cause x linked Nystagmus and variable xlmr phenotypes
European Journal of Human Genetics, 2010Co-Authors: Anna Hackett, Patrick S Tarpey, Andrea Licata, James J Cox, Annabel Whibley, Jackie Boyle, Carolyn J Rogers, John R Grigg, Michael Partington, Roger E StevensonAbstract:Mutations of the calcium/calmodulin-dependent serine protein kinase (CASK) gene have recently been associated with X-linked mental retardation (XLMR) with microcephaly, optic atrophy and brainstem and cerebellar hypoplasia, as well as with an X-linked syndrome having some FG-like features. Our group has recently identified four male probands from 358 probable XLMR families with missense mutations (p.Y268H, p.P396S, p.D710G and p.W919R) in the CASK gene. Congenital Nystagmus, a rare and striking feature, was present in two of these families. We screened a further 45 probands with either Nystagmus or microcephaly and mental retardation (MR), and identified two further mutations, a missense mutation (p.Y728C) and a splice mutation (c.2521-2A>T) in two small families with Nystagmus and MR. Detailed clinical examinations of all six families, including an ophthalmological review in four families, were undertaken to further characterise the phenotype. We report on the clinical features of 24 individuals, mostly male, from six families with CASK mutations. The phenotype was variable, ranging from non-syndromic mild MR to severe MR associated with microcephaly and dysmorphic facial features. Carrier females were variably affected. Congenital Nystagmus was found in members of four of the families. Our findings reinforce the CASK gene as a relatively frequent cause of XLMR in females and males. We further define the phenotypic spectrum and demonstrate that affected males with missense mutations or in-frame deletions in CASK are frequently associated with Congenital Nystagmus and XLMR, a striking feature not previously reported.
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mutations in frmd7 a newly identified member of the ferm family cause x linked idiopathic Congenital Nystagmus
Nature Genetics, 2006Co-Authors: Patrick S Tarpey, N Sarvananthan, Shery Thomas, Uma Mallya, Steven Lisgo, Christopher J Talbot, E O Roberts, M Awan, M Surendran, Rebecca J. McleanAbstract:Idiopathic Congenital Nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic Congenital Nystagmus. Screening of 42 singleton cases of idiopathic Congenital Nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.