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Sample records for cortico-basal ganglionic degeneration

  1. Longitudinal assessment of language and memory impairments in pathologically confirmed cortico-basal ganglionic degeneration.

    PubMed

    Tree, Jeremy J; Kay, Janice

    2008-10-01

    We report a longitudinal case study (patient EP) of histologically confirmed cortico-basal ganglionic degeneration (CBD) who presented with non-fluent progressive aphasia (NFPA). While NFPA has been documented in clinical descriptions of other reports of CBD, details are often limited and the majority of studies are cross-sectional in nature. The present study conducted detailed longitudinal assessment with EP over a period of two years that revealed substantial impairments of episodic memory, semantic memory, naming and particular aspects of reading and spelling. Our investigations identify key features of EP's pattern of impairment that warrant further examination with other cases of CBD. In particular, testing of EP's nonword reading and spelling found that both were impaired and declined over time. In addition, verbal recognition deteriorated faster than non-verbal recognition through the course of the disease. Our review of the literature suggests that poor nonword reading and spelling may be consistent features of CBD, but more studies are needed to confirm this suggestion, and to determine whether they warrant inclusion in profiling CBD. PMID:18761137

  2. The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography.

    PubMed Central

    Eidelberg, D; Dhawan, V; Moeller, J R; Sidtis, J J; Ginos, J Z; Strother, S C; Cederbaum, J; Greene, P; Fahn, S; Powers, J M

    1991-01-01

    Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life. Images PMID:1744638

  3. [Cortico-basal degeneration: the rare form of tau protein disease].

    PubMed

    Budrewicz, Sławomir; Koszewicz, Magdalena; Góral, Małgorzata; Słotwiński, Krzysztof; Podemski, Ryszard; Turek, Tomasz

    2003-01-01

    Cortico-basal degeneration is a rare degenerative disease connected with Tau protein pathology. Epidemiology of cortico-basal degeneration is unknown. The authors present a case of 59 years old woman with suspicion of cortico-basal degeneration. The extrapyramidal symptoms mainly on the right side with "alien limb phenomenon" and dystonia of lower limb is observed in our patient. Cortico-subcortical brain atrophy was present in MRI scans. EEG was asymmetrical. No improvement was noticed after L-Dopa. Treatment of amantidine caused the transient improvement. PMID:15098333

  4. Transcranial Magnetic Stimulation (TMS) as a Tool for Early Diagnosis and Prognostication in Cortico-Basal Ganglia Degeneration (CBD) Syndromes: Review of Literature and Case Report

    PubMed Central

    Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Nagaraju, B. C.

    2016-01-01

    Background: Cortico basal degeneration (CBD) of the brain is a rare progressive neurodegenerative disease which encompasses unique neuropsychiatric manifestations. Early diagnosis is essential for initiating proper treatment and favorable outcome. Transcranial Magnetic Stimulation (TMS), a well-known technique for assessment of cortical excitatory and inhibitory properties. It was suggested that in a degenerative disease like CBD which involves the cortex as well as the subcortical structures, comparing both hemispheres, a differential pattern in TMS can be obtained which would help in early identification, prognostication and early therapeutic intervention. Case Report: We describe a case of CBD with corroborative clinical and imaging picture wherein single pulse TMS was used over both the hemispheres measuring the following parameters of interest which included: Motor Threshold (MT), Central Motor Conduction Time (CMCT) and Silent Period (SP). Results and Conclusion: Differential patterns of MT, CMCT and SP was obtained by stimulating over both the hemispheres with the affected hemisphere showing significantly reduced MT and prolonged CMCT implying early impairment of cortical and subcortical structures thereby revealing the potential application of TMS being utilized in a novel way for early detection and prognostication in CBD syndromes. PMID:27011412

  5. Cortical Basal Ganglionic Degeneration

    PubMed Central

    Scarmeas, Nikolaos; Chin, Steven S.; Marder, Karen

    2011-01-01

    In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms. PMID:14602941

  6. Neural representation of time in cortico-basal ganglia circuits

    PubMed Central

    Jin, Dezhe Z.; Fujii, Naotaka; Graybiel, Ann M.

    2009-01-01

    Encoding time is universally required for learning and structuring motor and cognitive actions, but how the brain keeps track of time is still not understood. We searched for time representations in cortico-basal ganglia circuits by recording from thousands of neurons in the prefrontal cortex and striatum of macaque monkeys performing a routine visuomotor task. We found that a subset of neurons exhibited time-stamp encoding strikingly similar to that required by models of reinforcement-based learning: They responded with spike activity peaks that were distributed at different time delays after single task events. Moreover, the temporal evolution of the population activity allowed robust decoding of task time by perceptron models. We suggest that time information can emerge as a byproduct of event coding in cortico-basal ganglia circuits and can serve as a critical infrastructure for behavioral learning and performance. PMID:19850874

  7. Changes in ganglion cells during retinal degeneration.

    PubMed

    Saha, Susmita; Greferath, Ursula; Vessey, Kirstan A; Grayden, David B; Burkitt, Anthony N; Fletcher, Erica L

    2016-08-01

    Inherited retinal degeneration such as retinitis pigmentosa (RP) is associated with photoreceptor loss and concomitant morphological and functional changes in the inner retina. It is not known whether these changes are associated with changes in the density and distribution of synaptic inputs to retinal ganglion cells (RGCs). We quantified changes in ganglion cell density in rd1 and age-matched C57BL/6J-(wildtype, WT) mice using the immunocytochemical marker, RBPMS. Our data revealed that following complete loss of photoreceptors, (∼3months of age), there was a reduction in ganglion cell density in the peripheral retina. We next examined changes in synaptic inputs to A type ganglion cells by performing double labeling experiments in mice with the ganglion cell reporter lines, rd1-Thy1 and age-matched wildtype-Thy1. Ribbon synapses were identified by co-labelling with CtBP2 (RIBEYE) and conventional synapses with the clustering molecule, gephyrin. ON RGCs showed a significant reduction in RIBEYE-immunoreactive synapse density while OFF RGCs showed a significant reduction in the gephyrin-immmunoreactive synapse density. Distribution patterns of both synaptic markers across the dendritic trees of RGCs were unchanged. The change in synaptic inputs to RGCs was associated with a reduction in the number of immunolabeled rod bipolar and ON cone bipolar cells. These results suggest that functional changes reported in ganglion cells during retinal degeneration could be attributed to loss of synaptic inputs. PMID:27132232

  8. Degeneration and regeneration of ganglion cell axons.

    PubMed

    Weise, J; Ankerhold, R; Bähr, M

    2000-01-15

    The retino-tectal system has been used to study developmental aspects of axon growth, synapse formation and the establishment of a precise topographic order as well as degeneration and regeneration of adult retinal ganglion cell (RGC) axons after axonal lesion. This paper reviews some novel findings that provide new insights into the mechanisms of developmental RGC axon growth, pathfinding, and target formation. It also focuses on the cellular and molecular cascades that underlie RGC degeneration following an axonal lesion and on some therapeutic strategies to enhance survival of axotomized RGCs in vivo. In addition, this review deals with problems related to the induction of regeneration after axonal lesion in the adult CNS using the retino-tectal system as model. Different therapeutic approaches to promote RGC regeneration and requirements for specific target formation of regenerating RGCs in vitro and in vivo are discussed. PMID:10649506

  9. Functions of the cortico-basal ganglia circuits for spoken language may extend beyond emotional-affective modulation in adults.

    PubMed

    Hanakawa, Takashi; Hosoda, Chihiro

    2014-12-01

    We support Ackermann et al.'s proposal that the cortico-basal ganglia circuits may play essential roles in the evolution of spoken language. Here we discuss further evidence indicating that the cortico-basal ganglia circuits may contribute to various aspects of spoken language including planning, learning, and controlling of speech in adulthood.

  10. Coupling in the cortico-basal ganglia circuit is aberrant in the ketamine model of schizophrenia.

    PubMed

    Cordon, Ivan; Nicolás, María Jesús; Arrieta, Sandra; Lopetegui, Eneko; López-Azcárate, Jon; Alegre, Manuel; Artieda, Julio; Valencia, Miguel

    2015-08-01

    Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals׳ behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1-4; theta 4-8Hz) and the amplitude of high-gamma (~80Hz) and high-frequency oscillations (HFO) (~150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO's across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients.

  11. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    PubMed Central

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  12. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    PubMed

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

  13. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    PubMed

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  14. Overlapping connections within the motor cortico-basal ganglia circuit: fMRI-tractography analysis.

    PubMed

    Oguri, Takuya; Sawamoto, Nobukatsu; Tabu, Hayato; Urayama, Shin-ichi; Matsuhashi, Masao; Matsukawa, Noriyuki; Ojika, Kosei; Fukuyama, Hidenao

    2013-09-01

    Contribution of the subcortical nuclei to the coordination of human behavior is dependent on the existence of appropriate anatomical architecture. Interpretations of available data have led to opposing 'information funneling' and 'parallel processing' hypotheses. Using motor circuit as a model, we examined whether cortico-subcortical circuits, especially cortico-basal ganglia circuits, are funneled or parallel in the control of volitional movement. Twenty-five healthy subjects underwent functional magnetic resonance imaging (fMRI). Activated clusters during self-initiated, sequential finger-to-thumb opposition movements of the left hand were identified in the bilateral supplementary motor area (SMA), right lateral premotor cortex (PM) and primary motor cortex (M1), and in the right striatum and thalamus. These functionally defined clusters were applied to probabilistic tractography based on diffusion-weighted MRI to examine patterns of connectivity. Striatal and thalamic sub-regions with high probabilities of connection to the motor cortices partially overlapped, with connection to the two premotor areas outspreading rostrally relative to M1. We suggest that, on a macroscopic anatomical level, there is overlap as well as segregation among connections of the motor cortices with the striatum and thalamus. This supports the notion that neuronal information of the motor cortices is funneled, and parallel processing is not an exclusive principle in the basal ganglia.

  15. Identifying enhanced cortico-basal ganglia loops associated with prolonged dance training

    PubMed Central

    Li, Gujing; He, Hui; Huang, Mengting; Zhang, Xingxing; Lu, Jing; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

    2015-01-01

    Studies have revealed that prolonged, specialized training combined with higher cognitive conditioning induces enhanced brain alternation. In particular, dancers with long-term dance experience exhibit superior motor control and integration with their sensorimotor networks. However, little is known about the functional connectivity patterns of spontaneous intrinsic activities in the sensorimotor network of dancers. Our study examined the functional connectivity density (FCD) of dancers with a mean period of over 10 years of dance training in contrast with a matched non-dancer group without formal dance training using resting-state fMRI scans. FCD was mapped and analyzed, and the functional connectivity (FC) analyses were then performed based on the difference of FCD. Compared to the non-dancers, the dancers exhibited significantly increased FCD in the precentral gyri, postcentral gyri and bilateral putamen. Furthermore, the results of the FC analysis revealed enhanced connections between the middle cingulate cortex and the bilateral putamen and between the precentral and the postcentral gyri. All findings indicated an enhanced functional integration in the cortico-basal ganglia loops that govern motor control and integration in dancers. These findings might reflect improved sensorimotor function for the dancers consequent to long-term dance training. PMID:26035693

  16. Identifying enhanced cortico-basal ganglia loops associated with prolonged dance training.

    PubMed

    Li, Gujing; He, Hui; Huang, Mengting; Zhang, Xingxing; Lu, Jing; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

    2015-06-02

    Studies have revealed that prolonged, specialized training combined with higher cognitive conditioning induces enhanced brain alternation. In particular, dancers with long-term dance experience exhibit superior motor control and integration with their sensorimotor networks. However, little is known about the functional connectivity patterns of spontaneous intrinsic activities in the sensorimotor network of dancers. Our study examined the functional connectivity density (FCD) of dancers with a mean period of over 10 years of dance training in contrast with a matched non-dancer group without formal dance training using resting-state fMRI scans. FCD was mapped and analyzed, and the functional connectivity (FC) analyses were then performed based on the difference of FCD. Compared to the non-dancers, the dancers exhibited significantly increased FCD in the precentral gyri, postcentral gyri and bilateral putamen. Furthermore, the results of the FC analysis revealed enhanced connections between the middle cingulate cortex and the bilateral putamen and between the precentral and the postcentral gyri. All findings indicated an enhanced functional integration in the cortico-basal ganglia loops that govern motor control and integration in dancers. These findings might reflect improved sensorimotor function for the dancers consequent to long-term dance training.

  17. Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.

    PubMed

    Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

    2013-02-01

    Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction.

  18. Reward-guided learning beyond dopamine in the nucleus accumbens: The integrative functions of cortico-basal ganglia networks

    PubMed Central

    Yin, Henry H.; Ostlund, Sean B.; Balleine, Bernard W.

    2009-01-01

    Here we challenge the view that reward-guided learning is solely controlled by the mesoaccumbens pathway arising from dopaminergic neurons in the ventral tegmental area and projecting to the nucleus accumbens. This widely accepted view assumes that reward is a monolithic concept, but recent work has suggested otherwise. It now appears that, in reward-guided learning, the functions of ventral and dorsal striata, and the cortico-basal ganglia circuitry associated with them, can be dissociated. Whereas the nucleus accumbens is necessary for the acquisition and expression of certain appetitive Pavlovian responses and contributes to the motivational control of instrumental performance, the dorsal striatum is necessary for the acquisition and expression of instrumental actions. Such findings suggest the existence of multiple independent yet interacting functional systems that are implemented in iterating and hierarchically organized cortico-basal ganglia networks engaged in appetitive behaviors ranging from Pavlovian approach responses to goal-directed instrumental actions controlled by action-outcome contingencies. PMID:18793321

  19. Sudden death while driving. Role of sinus perinodal degeneration and cardiac neural degeneration and ganglionitis.

    PubMed

    James, T N; Pearce, W N; Givhan, E G

    1980-05-01

    A young business executive was seen to slump over his steering wheel while driving, after which the automobile veered and turned over. Quickly taken unconscious to a nearby emergency room, he was pronounced dead on arrival. Because there was insufficient physical injury found to account for his death, and because atrial fibrillation had been detected for the first time on a routine physical examination 3 months previously, special examination of the cardiac conduction system was performed. A fibroma was present on the right side of the central fibrous body above the His bundle, similar to several fibromas on the mitral valve. Small foci of neuritis were present in the ventricular myocardium and the atrioventricular node. More extensive neural degeneration and ganglionitis were found near the sinus node, which also exhibited an encircling perinodal fibrosis. Ways in which these abnormalities could have caused a fatal electrical instability of the heart are discussed. Careful examination of the cardiac conduction system is warranted in other fatal automobile accidents under similar circumstances.

  20. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

    NASA Astrophysics Data System (ADS)

    Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

    2016-04-01

    Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

  1. Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration

    PubMed Central

    Fernández-Sánchez, Laura; Rondón, Netxibeth; Esquiva, Gema; Germain, Francisco; de la Villa, Pedro; Cuenca, Nicolás

    2015-01-01

    Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss. PMID:26379056

  2. Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration.

    PubMed

    Gómez-Vicente, Violeta; Lax, Pedro; Fernández-Sánchez, Laura; Rondón, Netxibeth; Esquiva, Gema; Germain, Francisco; de la Villa, Pedro; Cuenca, Nicolás

    2015-01-01

    Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.

  3. Time-Lapse Retinal Ganglion Cell Dendritic Field Degeneration Imaged in Organotypic Retinal Explant Culture

    PubMed Central

    Johnson, Thomas V.; Oglesby, Ericka N.; Steinhart, Matthew R.; Cone-Kimball, Elizabeth; Jefferys, Joan; Quigley, Harry A.

    2016-01-01

    Purpose To develop an ex vivo organotypic retinal explant culture system suitable for multiple time-point imaging of retinal ganglion cell (RGC) dendritic arbors over a period of 1 week, and capable of detecting dendrite neuroprotection conferred by experimental treatments. Methods Thy1-YFP mouse retinas were explanted and maintained in organotypic culture. Retinal ganglion cell dendritic arbors were imaged repeatedly using confocal laser scanning microscopy. Maximal projection z-stacks were traced by two masked investigators and dendritic fields were analyzed for characteristics including branch number, size, and complexity. One group of explants was treated with brain derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) added to the culture media. Changes in individual dendritic fields over time were detected using pair-wise comparison testing. Results Retinal ganglion cells in mouse retinal explant culture began to degenerate after 3 days with 52.4% surviving at 7 days. Dendritic field parameters showed minimal change over 8 hours in culture. Intra- and interobserver measurements of dendrite characteristics were strongly correlated (Spearman rank correlations consistently > 0.80). Statistically significant (P < 0.001) dendritic tree degeneration was detected following 7 days in culture including: 40% to 50% decreases in number of branch segments, number of junctions, number of terminal branches, and total branch length. Scholl analyses similarly demonstrated a significant decrease in dendritic field complexity. Treatment of explants with BDNF+CNTF significantly attenuated dendritic field degeneration. Conclusions Retinal explant culture of Thy1-YFP tissue provides a useful model for time-lapse imaging of RGC dendritic field degeneration over a course of several days, and is capable of detecting neuroprotective amelioration of dendritic pruning within individual RGCs. PMID:26811145

  4. Rescuing axons from degeneration does not affect retinal ganglion cell death

    PubMed Central

    de Lima, S.; Mietto, B.S.; Paula, C.; Muniz, T.; Martinez, A.M.B.; Gardino, P.F.

    2016-01-01

    After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD), an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs) after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18) treated with an exogenous calpain inhibitor (20 mM) administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05) and an increase in the number of preserved fibers (P<0.05) 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage. PMID:27007653

  5. Spontaneous Oscillatory Rhythms in the Degenerating Mouse Retina Modulate Retinal Ganglion Cell Responses to Electrical Stimulation

    PubMed Central

    Goo, Yong Sook; Park, Dae Jin; Ahn, Jung Ryul; Senok, Solomon S.

    2016-01-01

    Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties. PMID:26793063

  6. Spontaneous Oscillatory Rhythms in the Degenerating Mouse Retina Modulate Retinal Ganglion Cell Responses to Electrical Stimulation.

    PubMed

    Goo, Yong Sook; Park, Dae Jin; Ahn, Jung Ryul; Senok, Solomon S

    2015-01-01

    Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties.

  7. Spontaneous Oscillatory Rhythms in the Degenerating Mouse Retina Modulate Retinal Ganglion Cell Responses to Electrical Stimulation.

    PubMed

    Goo, Yong Sook; Park, Dae Jin; Ahn, Jung Ryul; Senok, Solomon S

    2015-01-01

    Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties. PMID:26793063

  8. Striatal dopamine ramping may indicate flexible reinforcement learning with forgetting in the cortico-basal ganglia circuits.

    PubMed

    Morita, Kenji; Kato, Ayaka

    2014-01-01

    It has been suggested that the midbrain dopamine (DA) neurons, receiving inputs from the cortico-basal ganglia (CBG) circuits and the brainstem, compute reward prediction error (RPE), the difference between reward obtained or expected to be obtained and reward that had been expected to be obtained. These reward expectations are suggested to be stored in the CBG synapses and updated according to RPE through synaptic plasticity, which is induced by released DA. These together constitute the "DA=RPE" hypothesis, which describes the mutual interaction between DA and the CBG circuits and serves as the primary working hypothesis in studying reward learning and value-based decision-making. However, recent work has revealed a new type of DA signal that appears not to represent RPE. Specifically, it has been found in a reward-associated maze task that striatal DA concentration primarily shows a gradual increase toward the goal. We explored whether such ramping DA could be explained by extending the "DA=RPE" hypothesis by taking into account biological properties of the CBG circuits. In particular, we examined effects of possible time-dependent decay of DA-dependent plastic changes of synaptic strengths by incorporating decay of learned values into the RPE-based reinforcement learning model and simulating reward learning tasks. We then found that incorporation of such a decay dramatically changes the model's behavior, causing gradual ramping of RPE. Moreover, we further incorporated magnitude-dependence of the rate of decay, which could potentially be in accord with some past observations, and found that near-sigmoidal ramping of RPE, resembling the observed DA ramping, could then occur. Given that synaptic decay can be useful for flexibly reversing and updating the learned reward associations, especially in case the baseline DA is low and encoding of negative RPE by DA is limited, the observed DA ramping would be indicative of the operation of such flexible reward learning.

  9. Degeneration of spiral ganglion cells in the chinchilla after inner hair cell loss induced by carboplatin.

    PubMed

    Takeno, S; Wake, M; Mount, R J; Harrison, R V

    1998-01-01

    The anticancer drug carboplatin has been used to generate inner hair cell (IHC) lesions in the cochlea of chinchillas. This has provided a valuable model for the study of the relative roles of IHCs and outer hair cells (OHCs). In the present study, we examined the pathological and temporal relationships between the degeneration of the cochlear IHCs and type I spiral ganglion cells (SGCs). A single intravenous dose of 200 mg/m2 carboplatin produced extensive IHC loss with no apparent effect on the OHCs. The auditory brainstem response threshold was significantly elevated by 2 weeks following treatment and remained stable through 12 weeks. Elevated thresholds were well correlated with morphological lesions. On the other hand, the SGC population progressively decreased from 2 to 12 weeks after treatment, to about half of the control density values. A positive correlation existed between the density of SGC and the number of surviving IHCs. These results indicate that selective damage to IHCs causes a distinct loss of SGCs. PMID:9705525

  10. Spiral ganglion degeneration and hearing loss as a consequence of satellite cell death in saposin B-deficient mice.

    PubMed

    Akil, Omar; Sun, Ying; Vijayakumar, Sarath; Zhang, Wujuan; Ku, Tiffany; Lee, Chi-Kyou; Jones, Sherri; Grabowski, Gregory A; Lustig, Lawrence R

    2015-02-18

    Saposin B (Sap B) is an essential activator protein for arylsulfatase A in the hydrolysis of sulfatide, a lipid component of myelin. To study Sap B's role in hearing and balance, a Sap B-deficient (B(-/-)) mouse was evaluated. At both light and electron microscopy (EM) levels, inclusion body accumulation was seen in satellite cells surrounding spiral ganglion (SG) neurons from postnatal month 1 onward, progressing into large vacuoles preceding satellite cell degeneration, and followed by SG degeneration. EM also revealed reduced or absent myelin sheaths in SG neurons from postnatal month 8 onwards. Hearing loss was initially seen at postnatal month 6 and progressed thereafter for frequency-specific stimuli, whereas click responses became abnormal from postnatal month 13 onward. The progressive hearing loss correlated with the accumulation of inclusion bodies in the satellite cells and their subsequent degeneration. Outer hair cell numbers and efferent function measures (distortion product otoacoustic emissions and contralateral suppression) were normal in the B(-/-) mice throughout this period. Alcian blue staining of SGs demonstrated that these inclusion bodies corresponded to sulfatide accumulation. In contrast, changes in the vestibular system were much milder, but caused severe physiologic deficits. These results demonstrate that loss of Sap B function leads to progressive sulfatide accumulation in satellite cells surrounding the SG neurons, leading to satellite cell degeneration and subsequent SG degeneration with a resultant loss of hearing. Relative sparing of the efferent auditory and vestibular neurons suggests that alternate glycosphingolipid metabolic pathways predominate in these other systems.

  11. Attenuated infrared neuron stimulation response in cochlea of deaf animals may associate with the degeneration of spiral ganglion neurons

    PubMed Central

    Xie, Bingbin; Dai, Chunfu; Li, Huawei

    2015-01-01

    Hypothesis: We hypothesize that degenerated spiral ganglion neurons (SGNs) in guinea pigs reduces auditory brainstem responses evoked by pulsed infrared stimulation. Background: Pulsed infrared laser excitation can directly evoke physiological responses in neuronal and other excitable cells in vivo and in vitro. Laser pulses could benefit patients with cochlear implants to stimulate the auditory system. Methods: Pulsed infrared lasers were used to study evoked optical auditory brainstem responses (oABRs) in normal hearing and deafened animals. Aslo, the morphology and anatomy of SGNs in normal hearing and deafened guinea pigs were compared. Results: By recording oABRs evoked by varying infrared laser pulse durations, it is suggested that degeneration of SGNs in deafened guinea pigs was associated with an elevated oABR threshold and with lower amplitudes. Moreover, oABR threshold decreased while amplitudes increased in both normal hearing and deafened animals as the pulse duration prolonged. Electron microscopy revealed that SGNs in deafened guinea pigs had swollen and vacuolar mitochondria, as well as demyelinated soma and axons. Conclusion: Infrared laser pulses can stimulate SGNs to evoke oABRs in guinea pigs. Deafened guinea pigs have elevated thresholds and smaller amplitude responses, likely a result of degenerated SGNs. Short pulse durations are more suitable to evoke responses in both normal hearing and deafened animals. PMID:26114024

  12. Complimentary action: C1q increases ganglion cell survival in an in vitro model of retinal degeneration.

    PubMed

    Taylor, Linnéa; Arnér, Karin; Blom, Anna M; Ghosh, Fredrik

    2016-09-15

    Using a previously described retinal explant culture system as an acute injury model, we here explore the role of C1q, the initiator of the classical complement pathway, in neuronal cell survival and retinal homeostasis. Full-thickness adult rat retinal explants were divided into four groups, receiving the following supplementation: C1q (50nM), C1-inhibitor (C1-inh; Berinert; 500mg/l), C1q+C1-inh, and no supplementation (culture controls). Explants were kept for 12h or 2days after which they were examined morphologically and with a panel of immunohistochemical markers. C1q supplementation protects ganglion cells from degeneration within the explant in vitro system. This effect is correlated to an attenuated endogenous production of C1q, and a quiesced gliotic response. PMID:27609284

  13. Mitochondrial pathogenic mechanism and degradation in optineurin E50K mutation-mediated retinal ganglion cell degeneration

    PubMed Central

    Shim, Myoung Sup; Takihara, Yuji; Kim, Keun-Young; Iwata, Takeshi; Yue, Beatrice Y. J. T.; Inatani, Masaru; Weinreb, Robert N.; Perkins, Guy A.; Ju, Won-Kyu

    2016-01-01

    Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K−tg mice in vivo. While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro, it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro. These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress. PMID:27654856

  14. Human organotypic retinal cultures (HORCs) as a chronic experimental model for investigation of retinal ganglion cell degeneration.

    PubMed

    Osborne, Andrew; Hopes, Marina; Wright, Phillip; Broadway, David C; Sanderson, Julie

    2016-02-01

    There is a growing need for models of human diseases that utilise native, donated human tissue in order to model disease processes and develop novel therapeutic strategies. In this paper we assessed the suitability of adult human retinal explants as a potential model of chronic retinal ganglion cell (RGC) degeneration. Our results confirmed that RGC markers commonly used in rodent studies (NeuN, βIII Tubulin and Thy-1) were appropriate for labelling human RGCs and followed the expected differential expression patterns across, as well as throughout, the macular and para-macular regions of the retina. Furthermore, we showed that neither donor age nor post-mortem time (within 24 h) significantly affected the initial expression levels of RGC markers. In addition, the feasibility of using human post mortem donor tissue as a long-term model of RGC degeneration was determined with RGC protein being detectable up to 4 weeks in culture with an associated decline in RGC mRNA and significant, progressive, apoptotic labelling of NeuN(+) cells. Differences in RGC apoptosis might have been influenced by medium compositions indicating that media constituents could play a role in supporting axotomised RGCs. We propose that using ex vivo human explants may prove to be a useful model for testing the effectiveness of neuroprotective strategies.

  15. Axonal degeneration, regeneration and ganglion cell death in a rodent model of anterior ischemic optic neuropathy (rAION).

    PubMed

    Zhang, Cheng; Guo, Yan; Slater, Bernard J; Miller, Neil R; Bernstein, Steven L

    2010-08-01

    Using laser-induced photoactivation of intravenously administered rose Bengal in rats, we generated an ischemic infarction of the intrascleral portion of the optic nerve (ON) comparable to that which occurs in humans to investigate optic nerve axon degenerative events following optic nerve infarct and the potential for axon re-growth. Animals were euthanized at different times post infarct. Axon degeneration was evaluated with SMI312 immunolabeling, and GAP-43 immunostaining was used to identify axon regeneration. Terminal dUTP nick end labeling (TUNEL) was used to evaluate retinal ganglion cell (RGC) death. There was significant axon structural disruptinot ion at the anterior intrascleral portion of the ON by 3d post-infarct, extending to the posterior ON by 7d post-stroke. Destruction of normal axon structure and massive loss of axon fibers occurred by 2 weeks. GAP-43 immunoreactivity occurred in the anterior ON by 7d post-infarct, lasting 3-4 weeks, without extension past the primary ischemic lesion. TUNEL-positive cells in the RGC layer appeared by 7d post-insult. These results indicate that following induction of ischemic optic neuropathy, significant axon damage occurs by 3d post-infarct, with later neuronal death. Post-stroke adult rat retinal ganglion cells attempt to regenerate their axons, but this effort is restricted to the unmyelinated region of the anterior ON. These responses are important in understanding pathologic process that underlies human non-arteritic anterior ischemic optic neuropathy (NAION) and may guide both the appropriate treatment of NAION and the window of opportunity for such treatment. PMID:20621651

  16. The dark phase intraocular pressure elevation and retinal ganglion cell degeneration in a rat model of experimental glaucoma.

    PubMed

    Kwong, Jacky M K; Vo, Nancy; Quan, Ann; Nam, Michael; Kyung, Haksu; Yu, Fei; Piri, Natik; Caprioli, Joseph

    2013-07-01

    Intraocular pressure (IOP) elevation is considered as a major risk factor causing the progression of vision deterioration in glaucoma. Although it is known that the IOP level changes widely throughout the day and night, how the dark or light phase IOP elevation contributes to retinal ganglion cell (RGC) degeneration is still largely unclear. To examine the profile of IOP, modified laser photocoagulation was applied to the trabecular meshwork of Brown Norway rats and both light and dark phase IOPs were monitored approximately 1-2 times a week. The relationship between IOP elevation and RGC degeneration was investigated while RGC body loss was analyzed with Rbpms immunolabeling on retinal wholemount and axonal injury in the optic nerve was semi-quantified. The baseline awake dark and light IOPs were 30.4 ± 2.7 and 20.2 ± 2.1 mmHg respectively. The average dark IOP was increased to 38.2 ± 3.2 mmHg for five weeks after the laser treatment on 270° trabecular meshwork. However, there was no significant loss of RGC body and axonal injury. After laser treatment on 330° trabecular meshwork, the dark and light IOPs were significantly increased to 43.8 ± 4.6 and 23 ± 3.7 mmHg respectively for 5 weeks. The cumulative dark and light IOP elevations were 277 ± 86 and 113 ± 50 mmHg days respectively while the cumulative total (light and dark) IOP elevation was 213 ± 114 mmHg days. After 5 weeks, regional RGC body loss of 29.5 ± 15.5% and moderate axonal injury were observed. Axonal injury and loss of RGC body had a high correlation with the cumulative total IOP elevation (R(2) = 0.60 and 0.65 respectively). There was an association between the cumulative dark IOP elevation and RGC body loss (R(2) = 0.37) and axonal injury (R(2) = 0.51) whereas the associations between neuronal damages and the cumulative light IOP elevation were weak (for RGC body loss, R(2) = 0.01; for axonal injury, R(2) = 0.26). Simple linear regression model

  17. Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice

    PubMed Central

    Chi, Zai-Long; Yasumoto, Fumie; Sergeev, Yuri; Minami, Masayoshi; Obazawa, Minoru; Kimura, Itaru; Takada, Yuichiro; Iwata, Takeshi

    2010-01-01

    Primary open-angle glaucoma (POAG) is one of the three principal subtypes of glaucoma and among the leading cause of blindness worldwide. POAG is defined by cell death of the retinal ganglion cells (RGCs) and surrounding neuronal cells at higher or normal intraocular pressure (IOP). Coded by one of the three genes responsible for POAG, WD repeat-containing protein 36 (WDR36) has two domains with a similar folding. To address whether WDR36 is functionally important in the retina, we developed four transgenic mice strains overexpressing a wild-type (Wt) and three mutant variants of D606G, deletion of amino acids at positions 605–607 (Del605–607) and at 601–640 (Del601–640) equivalent to the location of the D658G mutation observed in POAG patients. A triple amino acid deletion of mouse Wdr36 at positions 605–607 corresponding to the deletion at positions 657–659 in humans developed progressive retinal degeneration at the peripheral retina with normal IOP. RGCs and connecting amacrine cell synapses were affected at the peripheral retina. Axon outgrowth rate of cultured RGC directly isolated from transgenic animal was significantly reduced by the Wdr36 mutation compared with Wt. Molecular modeling of wild and mutant mouse Wdr36 revealed that deletion at positions 605–607 removed three residues and a hydrogen bond, required to stabilize anti-parallel β-sheet of the 6th β-propeller in the second domain. We concluded that WDR36 plays an important functional role in the retina homeostasis and mutation to this gene can cause devastating retinal damage. These data will improve understanding of the functional property of WDR36 in the retina and provide a new animal model for glaucoma therapeutics. PMID:20631153

  18. Glaucoma-induced degeneration of retinal ganglion cells prevented by hypoxic preconditioning: a model of glaucoma tolerance.

    PubMed

    Zhu, Yanli; Zhang, Lihong; Schmidt, Jimena F; Gidday, Jeffrey M

    2012-01-01

    Like all cells, neurons adapt to stress by transient alterations in phenotype, an epigenetic response that forms the basis for preconditioning against acute ischemic injury in the central nervous system. We recently showed that a modified repetitive hypoxic preconditioning (RHP) regimen significantly extends the window of ischemic tolerance to acute retinal ischemic injury from days to months. The present study was undertaken to determine if this uniquely protracted neuroprotective phenotype would also confer resistance to glaucomatous neurodegeneration. Retinal ganglion cell death at somatic and axonal levels was assessed after both 3 and 10 wks of sustained intraocular hypertension in an adult mouse model of inducible, open-angle glaucoma, with or without RHP before intraocular pressure elevation. Loss of brn3-positive ganglion cell soma after 3 wks of experimental glaucoma, along with increases in several apoptotic endpoints, were all significantly and robustly attenuated in mice subjected to RHP. Soma protection by RHP was also confirmed after 10 wks of intraocular hypertension by brn3 and SMI32 immunostaining. In addition, quantification of axon density in the postlaminar optic nerve documented robust preservation in RHP-treated mice, and neurofilament immunostaining also revealed preconditioning-induced improvements in axon integrity/survival in both retina and optic nerve after 10 wks of experimental glaucoma. This uniquely protracted period of phenotypic change, established in retinal ganglion cells by the activation of latent antiapoptotic, prosurvival mechanisms at both somatic and axonal levels, reflects a novel form of inducible neuronal plasticity that may provide innovative therapeutic targets for preventing and treating glaucoma and other neurodegenerative diseases. PMID:22396016

  19. Rotenone causing dysfunctional mitochondria and lysosomes in cerebral ganglions of Lumbricus terrestris degenerate giant fibers and neuromuscular junctions.

    PubMed

    Subaraja, Mamangam; Vanisree, Arambakkam Janardhanam

    2016-06-01

    Rotenone is well-documented to cause neurodegenerative condition such as Parkinson's, in the exposed systems. However, its detrimental effect on particular sites of neuronal pathway is still under investigation. We aimed at elucidating the impact of rotenone on cerebral ganglions (CG) of Lumbricus terrestris which control movement and behaviour of the worms. Worms were exposed to 0-0.4 ppm/mL of rotenone. Mitochondrial and lysosomal integrities were found to be affected beyond 0.2 ppm/mL of rotenone. Activities of cholinergic enzymes and the expression of tyrosine hydroxylase showed an impaired neuronal transmission in CGs at the dose of 0.2 ppm/mL of rotenone. Histopathological and immunoflourescent analyses showed neuronal apoptosis, reduced nucleic acid content and inhibited of neurosecretion at 0.3 ppm/mL. Electron microscopy showed that the neurons and neuromuscular junctions were affected at 0.2 ppm/mL. Dose-dependent changes were also observed in the motor function such as burrowing behaviours and locomotion. Conduction velocity (CV) and locomotion assessment showed that the CV of lateral giant fiber (LGF) was reduced while that of MGF remains unaffected at 0.2 ppm, the dose at which the burrowing behaviour was also not affected. LGF, cholinergic enzymes and tyrosine hydroxylase are primarily targeted by rotenone affecting locomotion at 0.2 ppm/mL while MGF, neuropile and the burrowing behaviour were affected at 0.3 ppm/mL. We demonstrate, in addition to dose-dependent effects, that the bioaccumulation factors range 0.28-0.32 ppm/μg of rotenone cause degenerative impact on giant fibers affecting neuronal behaviors/locomotion of worms. We also propose worms for studying mechanisms of neuronal pathology caused by chemicals prevailing in earth's atmosphere. PMID:27003369

  20. The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report

    PubMed Central

    Ozturk, Cengiz; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yolas, Coskun; Kabalar, Mehmet Esref; Gundogdu, Betul; Duman, Aslihan; Kanat, Ilyas Ferit; Gundogdu, Cemal

    2015-01-01

    Context: Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. Aims: The goal of this study was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar subarachnoid hemorrhage (SAH) on bowel dilatation severity. Settings and Design: An experimental rabbit study. Materials and Methods: The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13), serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. Results: The mean volume of imaginary descending colons was estimated as 93 ± 12 cm3 in the control group and 121 ± 26 cm3 in the SS group and 176 ± 49 cm3 in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05). Conclusion: An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies. PMID:25972712

  1. Symptomatic intratendinous ganglion cyst of the patellar tendon.

    PubMed

    Jose, Jean; O'Donnell, Kevin; Lesniak, Bryson

    2011-01-01

    Ganglion cysts have been previously described throughout the body, most commonly about the wrist, hand, knee, ankle, and feet. When symptomatic, they may interfere with joint mechanics, resulting in snapping, catching, and locking. Intratendinous ganglion cysts lack a synovial epithelial lining and are thought to develop from the mucoid degeneration of connective tissue caused by chronic irritation, chronic repetitive injury, and chronic ischemia. On magnetic resonance imaging, ganglion cysts originating from tendons, ligaments, tendon sheaths, menisci, or joint capsules appear as well-defined lobulated masses that follow simple or complex fluid signal intensity on all pulse sequences, with enhancing walls and internal septations on post-contrast images. There may be appreciable degeneration and partial tearing of the structure of origin, particularly if associated with tendons. On ultrasonography, they present as hypoechoic masses, with internal septations and lobulations of varying sizes, without significant vascularity on power or color Doppler sampling. A thin fluid neck extending from the structure of origin (tail sign), when present, is a reliable sign of a ganglion cyst. This article describes a sonographically guided technique to treat symptomatic ganglion cysts within the patellar tendon. Complete evacuation of the ganglion cyst, with disappearance of the tail sign, is considered the determining factor for a successful procedure. A similar technique can be used for the treatment of other symptomatic intratendinous ganglion cysts elsewhere in the body. To our knowledge, symptomatic intratendinous ganglion cysts within the patellar tendon and their treatment have not been previously reported.

  2. Cardiac ganglionitis associated with sudden unexpected death.

    PubMed

    James, T N; Zipes, D P; Finegan, R E; Eisele, J W; Carter, J E

    1979-11-01

    In a postmortem study of the hearts of two young women who died suddenly and unexpectedly, we found a remarkably similar and distinctive ganglionitis, predominantly in the region of the sinus node. Both women had ventricular fibrillation at the time of collapse. Vesicular neuritis and older neural degeneration were present in other regions of the heart. Except for focal fibromuscular dysplasia of the sinus node artery and atrioventricular node artery of one heart, there was no other significant anatomic abnormality in either heart. The functional significance of this cardiac ganglionitis is unclear, but its location in and around the conduction system makes it a possible cause of the fatal electrical instability. Recognition that ganglionitis of the heart may be associated with sudden death should stimulate a number of additionally useful studies.

  3. Macular degeneration

    MedlinePlus

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  4. Cerebellar Degeneration

    MedlinePlus

    ... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

  5. Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjögren's syndrome.

    PubMed

    Malinow, K; Yannakakis, G D; Glusman, S M; Edlow, D W; Griffin, J; Pestronk, A; Powell, D L; Ramsey-Goldman, R; Eidelman, B H; Medsger, T A

    1986-10-01

    Sensory neuropathies, particularly trigeminal neuropathy, have been recognized as neurological complications of Sjögren's syndrome, but the pathogenesis has not been established. We describe a woman with primary Sjögren's syndrome who developed a progressive debilitating subacute sensory neuronopathy. Results of electrophysiological studies were consistent with involvement of the trigeminal and dorsal root ganglia. A thoracic dorsal root ganglion biopsy showed lymphocytic infiltration and degeneration of ganglion cells. We believe that this is the first description of biopsy-documented dorsal root ganglionitis in a subacute sensory neuronopathy associated with Sjögren's syndrome and that the finding suggests an immunopathogenic basis.

  6. Macular Degeneration

    MedlinePlus

    ... common early symptom. Dry AMD happens when the light-sensitive cells in the macula slowly break down. Your gradually lose your central vision. A common early symptom is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease ...

  7. The place of dopamine in the cortico-basal ganglia circuit.

    PubMed

    Haber, S N

    2014-12-12

    The midbrain dopamine (DA) neurons play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. Indeed, subpopulations of DA neurons have been associated with these different functions: the mesolimbic, mesocortical, and nigrostriatal pathways. The mesolimbic and nigrostriatal pathways are an integral part of the basal ganglia through its reciprocal connections to the ventral and dorsal striatum respectively. This chapter reviews the connections of the midbrain DA cells and their role in integrating information across limbic, cognitive and motor functions. Emphasis is placed on the interface between these functional domains within the striatum through corticostriatal connections, through the striato-nigro-striatal connection, and through the lateral habenula projection to the midbrain.

  8. Switching from automatic to controlled behavior: cortico-basal ganglia mechanisms

    PubMed Central

    Hikosaka, Okihide; Isoda, Masaki

    2010-01-01

    Although we carry out most daily tasks nearly automatically, it is occasionally necessary to change a routine if something changes in our environment and the behavior becomes inappropriate. Such behavioral switching can occur either retroactively based on error feedback or proactively by detecting a contextual cue. Recent imaging and electrophysiological data in humans and monkeys have suggested that the frontal cortical areas play executive roles in behavioral switching. The anterior cingulate cortex acts retroactively and the pre-supplementary motor area acts proactively to enable behavioral switching. The lateral prefrontal cortex reconfigures cognitive processes constituting the switched behavior. The subthalamic nucleus and the striatum in the basal ganglia mediate these cortical signals to achieve behavioral switching. We discuss how breaking a routine to allow more adaptive behavior requires a fine-tuned recruitment of the frontal cortical-basal ganglia neural network. PMID:20181509

  9. The place of dopamine in the cortico-basal ganglia circuit.

    PubMed

    Haber, S N

    2014-12-12

    The midbrain dopamine (DA) neurons play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. Indeed, subpopulations of DA neurons have been associated with these different functions: the mesolimbic, mesocortical, and nigrostriatal pathways. The mesolimbic and nigrostriatal pathways are an integral part of the basal ganglia through its reciprocal connections to the ventral and dorsal striatum respectively. This chapter reviews the connections of the midbrain DA cells and their role in integrating information across limbic, cognitive and motor functions. Emphasis is placed on the interface between these functional domains within the striatum through corticostriatal connections, through the striato-nigro-striatal connection, and through the lateral habenula projection to the midbrain. PMID:25445194

  10. EVALUATION OF HYPERALGESIA AND HISTOLOGICAL CHANGES OF DORSAL ROOT GANGLION INDUCED BY NUCLEUS PULPOSUS

    PubMed Central

    Grava, André Luiz de Souza; Ferrari, Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido

    2015-01-01

    To evaluate the hyperalgesia and histological abnormalities induced by contact between the dorsal root ganglion and the nucleus pulposus. Methods: Twenty Wistar rats were used, divided into two experimental groups. In one of the groups, a fragment of autologous nucleus pulposus was removed from the sacrococcygeal region and deposited on the L5 dorsal root ganglia. In the other group (control), a fragment of adipose tissue was deposited on the L5 dorsal root ganglia. Mechanical and thermal hyperalgesia was evaluated on the third day and the first, third, fifth and seventh weeks after the operation. A L5 dorsal root ganglion was removed in the first, third, fifth and seventh weeks after the operation for histological study using HE staining and histochemical study using specific labeling for iNOS. Results: Higher intensity of mechanical and thermal hyperalgesia was observed in the group of animals in which the nucleus pulposus was placed in contact with the dorsal root ganglion. In this group, the histological study showed abnormalities of the dorsal root ganglion tissue, characterized by an inflammatory process and axonal degeneration. The histopathological abnormalities of the dorsal root ganglion tissue presented increasing intensity with increasing length of observation, and there was a correlation with maintenance of the hyperalgesia observed in the behavioral assessment. Immunohistochemistry using specific labeling for iNOS in the group of animals in which the nucleus pulposus was placed in contact with the dorsal root ganglion showed higher expression of this enzyme in the nuclei of the inflammatory cells (glial cells) surrounding the neurons. Conclusion: Contact between the nucleus pulposus and the dorsal root ganglion induced mechanical and thermal hyperalgesia and caused histological abnormalities in the dorsal root ganglion components. These abnormalities were characterized by an inflammatory and degenerative process in the structures of the dorsal root

  11. Macular degeneration (image)

    MedlinePlus

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  12. American Macular Degeneration Foundation

    MedlinePlus

    ... to content Contact DONATE Search for: Search Saving sight through research and education American Macular Degeneration Foundation Saving Sight Through Research and Education Menu About Macular Degeneration ...

  13. Optic pathway degeneration in Japanese black cattle.

    PubMed

    Chiba, Shiori; Funato, Shingo; Horiuchi, Noriyuki; Matsumoto, Kotaro; Inokuma, Hisashi; Furuoka, Hidefumi; Kobayashi, Yoshiyasu

    2015-02-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy. PMID:25421501

  14. Optic pathway degeneration in Japanese black cattle.

    PubMed

    Chiba, Shiori; Funato, Shingo; Horiuchi, Noriyuki; Matsumoto, Kotaro; Inokuma, Hisashi; Furuoka, Hidefumi; Kobayashi, Yoshiyasu

    2015-02-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.

  15. [Hepatolenticular degeneration].

    PubMed

    Zudenigo, D; Relja, M

    1990-01-01

    Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the

  16. Synaptic transmission in the superior cervical ganglion of the cat after reinnervation by vagus fibres

    PubMed Central

    Ceccarelli, B.; Clementi, F.; Mantegazza, P.

    1971-01-01

    1. A vagus-sympathetic anastomosis was performed in the cat by connecting end to end the cranial trunk of the vagus to the cranial end of the cervical sympathetic trunk, both severed under the ganglia. 2. Forty to sixty days after the anastomosis, the ocular signs of sympathetic paralysis (such as myosis and prolapse of the nictitating membrane) which had developed shortly after the operation, had completely disappeared, thus suggesting the recovery of synaptic transmission in the ganglion. In case of plain preganglionic denervation after the same period the ocular signs of cervical sympathetic paralysis were still present. 3. Contraction of the nictitating membrane could be induced by electrical stimulation of both the vagus preanastomotic and the sympathetic postanastomotic—preganglionic trunks. Ganglionic blocking agents induced the blockade of the `new' ganglionic synaptic function, while nicotine and pilocarpine provoked a marked contraction of the nictitating membrane. 4. Electron microscopy showed that the preganglionic regeneration of vagus fibers resulted in the formation of new synapses, mainly of axodendritic type, identical to normal ganglionic synapses. Moreover, after cutting the preanastomotic trunk of the vagus, these new ganglionic presynaptic profiles degenerated, thus proving their vagal origin. 5. During restoration of the synaptic contacts readjustment of dendritic tips occurred. ImagesText-fig. 2Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 16Fig. 17Fig. 14Fig. 15Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 7Fig. 8 PMID:4326851

  17. Macular Degeneration Partnership

    MedlinePlus

    AMD Macular Degeneration Partnership High Contrast Original + Font Size – Home About AMD Dry AMD Wet AMD Experience AMD Living with ... vision on a daily basis. AMD (Age Related Macular Degeneration) Partnership Listen AMD Month Public Service Announcement To ...

  18. Proximal Sciatic Nerve Intraneural Ganglion Cyst

    PubMed Central

    Swartz, Karin R.; Wilson, Dianne; Boland, Michael; Fee, Dominic B.

    2009-01-01

    Intraneural ganglion cysts are nonneoplastic, mucinous cysts within the epineurium of peripheral nerves which usually involve the peroneal nerve at the knee. A 37-year-old female presented with progressive left buttock and posterior thigh pain. Magnetic resonance imaging revealed a sciatic nerve mass at the sacral notch which was subsequently revealed to be an intraneural ganglion cyst. An intraneural ganglion cyst confined to the proximal sciatic nerve has only been reported once prior to 2009. PMID:20069041

  19. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  20. Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells

    PubMed Central

    Tochitsky, Ivan; Polosukhina, Aleksandra; Degtyar, Vadim E.; Gallerani, Nicholas; Smith, Caleb M.; Friedman, Aaron; Van Gelder, Russell N.; Trauner, Dirk; Kaufer, Daniela; Kramer, Richard H.

    2014-01-01

    Summary Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. Here we report a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight. A single intraocular injection of DENAQ photosensitizes the blind retina for days, restoring electrophysiological and behavioral responses with no toxicity. Experiments on mouse strains with functional, non-functional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated photoreceptors. DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD. PMID:24559673

  1. The role of autophagy in axonal degeneration of the optic nerve.

    PubMed

    Koch, Jan Christoph; Lingor, Paul

    2016-03-01

    Different pathological conditions including glaucoma, optic neuritis, hereditary optic atrophy and traumatic injury lead to a degeneration of retinal ganglion cell axons in the optic nerve. Besides this clinical relevance, several experimental models employ the optic nerve as a model system to examine general mechanisms of axonal degeneration in the central nervous system. Several experimental studies have demonstrated that an activation of autophagy is a prominent feature of axonal degeneration in the optic nerve independent of the underlying pathological condition. However, the function of autophagy in axonal degeneration remains still unclear. Inhibition of autophagy was found to attenuate axonal degeneration within the first hours after optic nerve lesion. Other studies focusing on survival of retinal ganglion cells at later postlesional time points report contradicting results, where both inhibition and induction of autophagy were beneficial for survival, depending on the model system or examination time. Therefore, a more precise understanding of the role and the kinetics of autophagy in axonal degeneration is mandatory to develop new therapies for diseases of the optic nerve. Here, we review the literature on the pathophysiological role of autophagy in axonal degeneration in the optic nerve and discuss its implications for future therapeutic approaches in diseases of the eye and the central nervous system involving axonal degeneration.

  2. Neural remodeling in retinal degeneration.

    PubMed

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  3. Fine structure of the ganglion of Cephalodiscus gracilis (Pterobranchia, Hemichordata).

    PubMed

    Rehkämper, G; Welsch, U; Dilly, P N

    1987-05-01

    The ganglion of Cephalodiscus gracilis M'Intosh 1882 is entirely intraepithelial and located in the dorsal epidermis immediately behind the tentacular apparatus that is formed by the mesosome (collar). A characteristic feature of the ganglion is a well-developed neuropile in which different types of nerve fibres can be discerned, many of which contain small granules with electron-dense contents. There are no glia-like cells in association with these fibres. Only slender basal processes of epidermal epithelial cells traverse the neuropile. In the depth of the epithelium the neuropile borders the epidermal basal lamina; apically it is covered by a layer of cell bodies, the majority of which belong to what appear to be ordinary ciliated epidermal cells. Besides these epidermal cells the perikarya of two additional types of cells, which are considered to be neurons, can be discerned. One type is characterised by many rough endoplasmic reticulum cisterns and mitochondria, the other by abundant small, electron-dense granules. The nuclei of these cells are comparatively pale and contain a prominent nucleolus. The neuron cell bodies do not form a distinct layer; but they are loosely distributed somewhat deeper than those of the ordinary epidermal cells. They probably send off an apical process to the epidermal surface and a basally directed one into the neuropile. The ganglion has been compared to the nervous systems in cnidarians, some spiralians, and especially other hemichordates, echinoderms, and chordates; it is found to be of primitive rather than degenerate nature. Furthermore, the possible functional significance of its close connection to the food-capturing tentacular apparatus is discussed. PMID:3584559

  4. Fine structure of the ganglion of Cephalodiscus gracilis (Pterobranchia, Hemichordata).

    PubMed

    Rehkämper, G; Welsch, U; Dilly, P N

    1987-05-01

    The ganglion of Cephalodiscus gracilis M'Intosh 1882 is entirely intraepithelial and located in the dorsal epidermis immediately behind the tentacular apparatus that is formed by the mesosome (collar). A characteristic feature of the ganglion is a well-developed neuropile in which different types of nerve fibres can be discerned, many of which contain small granules with electron-dense contents. There are no glia-like cells in association with these fibres. Only slender basal processes of epidermal epithelial cells traverse the neuropile. In the depth of the epithelium the neuropile borders the epidermal basal lamina; apically it is covered by a layer of cell bodies, the majority of which belong to what appear to be ordinary ciliated epidermal cells. Besides these epidermal cells the perikarya of two additional types of cells, which are considered to be neurons, can be discerned. One type is characterised by many rough endoplasmic reticulum cisterns and mitochondria, the other by abundant small, electron-dense granules. The nuclei of these cells are comparatively pale and contain a prominent nucleolus. The neuron cell bodies do not form a distinct layer; but they are loosely distributed somewhat deeper than those of the ordinary epidermal cells. They probably send off an apical process to the epidermal surface and a basally directed one into the neuropile. The ganglion has been compared to the nervous systems in cnidarians, some spiralians, and especially other hemichordates, echinoderms, and chordates; it is found to be of primitive rather than degenerate nature. Furthermore, the possible functional significance of its close connection to the food-capturing tentacular apparatus is discussed.

  5. Purification of Dorsal Root Ganglion Neurons from Rat by Immunopanning

    PubMed Central

    Zuchero, J. Bradley

    2015-01-01

    Dorsal root ganglion neurons (DRGs) are sensory neurons that facilitate somatosensation and have been used to study neurite outgrowth, regeneration, and degeneration and PNS and CNS myelination. Studies of DRGs have relied on cell isolation strategies that generally involve extended culture in the presence of antimitotic agents or other cytotoxic treatments that target dividing cells. The surviving cells typically are dependent on serum for growth. Other methods, involving purification of DRGs based on their large size, produce low yield. In contrast, the immunopanning-based method described here for prospective isolation of DRGs from rodents allows for rapid purification in the absence of antimitotic agents and serum. These DRG cultures take place in a defined medium. They are free of Schwann cells and other glia and thus can be used to study the role of glia in the biology of DRG neurons. PMID:25086011

  6. Effects of low level laser treatment on the survival of axotomized retinal ganglion cells in adult Hamsters

    PubMed Central

    So, Kwok-Fai; Leung, Mason Chin Pang; Cui, Qi

    2014-01-01

    Injury to axons close to the neuronal bodies in the mammalian central nervous system causes a large proportion of parenting neurons to degenerate. It is known that optic nerve transection close to the eye in rodents leads to a loss of about half of retinal ganglion cells in 1 week and about 90% in 2 weeks. Using low level laser treatment in the present study, we demonstrated that treatment with helium-neon (660 nm) laser with 15 mW power could delay retinal ganglion cell death after optic nerve axotomy in adult hamsters. The effect was most apparent in the first week with a short period of treatment time (5 minutes) in which 65–66% of retinal ganglion cells survived the optic nerve axotomy whereas 45–47% of retinal ganglion cells did so in optic nerve axotomy controls. We also found that single dose and early commencement of laser irradiation were important in protecting retinal ganglion cells following optic nerve axotomy. These findings thus convincingly show that appropriate laser treatment may be neuroprotective to retinal ganglion cells. PMID:25558230

  7. Effects of low level laser treatment on the survival of axotomized retinal ganglion cells in adult Hamsters.

    PubMed

    So, Kwok-Fai; Leung, Mason Chin Pang; Cui, Qi

    2014-11-01

    Injury to axons close to the neuronal bodies in the mammalian central nervous system causes a large proportion of parenting neurons to degenerate. It is known that optic nerve transection close to the eye in rodents leads to a loss of about half of retinal ganglion cells in 1 week and about 90% in 2 weeks. Using low level laser treatment in the present study, we demonstrated that treatment with helium-neon (660 nm) laser with 15 mW power could delay retinal ganglion cell death after optic nerve axotomy in adult hamsters. The effect was most apparent in the first week with a short period of treatment time (5 minutes) in which 65-66% of retinal ganglion cells survived the optic nerve axotomy whereas 45-47% of retinal ganglion cells did so in optic nerve axotomy controls. We also found that single dose and early commencement of laser irradiation were important in protecting retinal ganglion cells following optic nerve axotomy. These findings thus convincingly show that appropriate laser treatment may be neuroprotective to retinal ganglion cells. PMID:25558230

  8. Tissue Engineering the Retinal Ganglion Cell Nerve Fiber Layer

    PubMed Central

    Kador, Karl E.; Montero, Ramon B.; Venugopalan, Praseeda; Hertz, Jonathan; Zindell, Allison N.; Valenzuela, Daniel A.; Uddin, Mohammed S.; Lavik, Erin B.; Muller, Kenneth J.; Andreopoulos, Fotios M.; Goldberg, Jeffrey L.

    2013-01-01

    Retinal degenerative diseases, such as glaucoma and macular degeneration, affect millions of people worldwide and ultimately lead to retinal cell death and blindness. Cell transplantation therapies for photoreceptors demonstrate integration and restoration of function, but transplantation into the ganglion cell layer is more complex, requiring guidance of axons from transplanted cells to the optic nerve head in order to reach targets in the brain. Here we create a biodegradable electrospun (ES) scaffold designed to direct the growth of retinal ganglion cell (RGC) axons radially, mimicking axon orientation in the retina. Using this scaffold we observed an increase in RGC survival and no significant change in their electrophysiological properties. When analyzed for alignment, 81% of RGCs were observed to project axons radially along the scaffold fibers, with no difference in alignment compared to the nerve fiber layer of retinal explants. When transplanted onto retinal explants, RGCs on ES scaffolds followed the radial pattern of the host retinal nerve fibers, whereas RGCs transplanted directly grew axons in a random pattern. Thus, the use of this scaffold as a cell delivery device represents a significant step towards the use of cell transplant therapies for the treatment of glaucoma and other retinal degenerative diseases. PMID:23489919

  9. Effects of metal ions on fibroblasts and spiral ganglion cells.

    PubMed

    Paasche, G; Ceschi, P; Löbler, M; Rösl, C; Gomes, P; Hahn, A; Rohm, H W; Sternberg, K; Lenarz, T; Schmitz, K-P; Barcikowski, S; Stöver, T

    2011-04-01

    Degeneration of spiral ganglion cells (SGC) after deafness and fibrous tissue growth around the electrode carrier after cochlear implantation are two of the major challenges in current cochlear implant research. Metal ions are known to possess antimicrobial and antiproliferative potential. The use of metal ions could therefore provide a way to reduce tissue growth around the electrode array after cochlear implantation. Here, we report on in vitro experiments with different concentrations of metal salts with antiproliferative and toxic effects on fibroblasts, PC-12 cells, and freshly isolated spiral ganglion cells, the target cells for electrical stimulation by a cochlear implant. Standard cell lines (NIH/3T3 and L-929 fibroblasts and PC-12 cells) and freshly isolated SGC were incubated with concentrations of metal ions between 0.3 μmol/liter and 10 mmol/liter for 48 hr. Cell survival was investigated by neutral red uptake, CellQuantiBlue assay, or counting of stained surviving neurons. Silver ions exhibited distinct thresholds for proliferating and confluent cells. For zinc ions, the effective concentration was lower for fibroblasts than for PC-12 cells. SGC showed comparable thresholds for reduced cell survival not only for silver and zinc ions but also for copper(II) ions, indicating that these ions might be promising for reducing tissue growth on the surface of CI electrode arrays. These effects were also observed when combinations of two of these ions were investigated. PMID:21312225

  10. The three faces of vestibular ganglionitis.

    PubMed

    Gacek, Richard R; Gacek, Mark R

    2002-02-01

    We present temporal bone and clinical evidence that common syndromes of recurrent vertigo are caused by a viral infection of the vestibular ganglion. In the present series, histopathologic and radiologic changes in the vestibular ganglion and meatal ganglion were consistent with a viral inflammation of ganglion cells in cases of Meniere's disease, benign paroxysmal positional vertigo, and vestibular neuronitis. Clinical observations of multiple neuropathies involving cranial nerves V, VII, and VIII on the same side in patients with recurrent vertigo are best explained by a cranial polyganglionitis caused by a neurotrophic virus, which is reactivated by a stressful event later in life. The reactivation of the latent virus may manifest as one of the above vertigo syndromes, depending on the part of the vestibular ganglion that is inflamed, the type and strain of the virus, and host resistance.

  11. Intrinsically photosensitive retinal ganglion cells.

    PubMed

    Do, Michael Tri Hoang; Yau, King-Wai

    2010-10-01

    Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors. PMID:20959623

  12. Ultrasound-guided aspiration and steroid injection of a posterior cruciate ligament ganglion cyst: report of a case.

    PubMed

    Vilella, Giuseppe Maria; Guerrisi, Pietro; Lucignani, Giulia; Pasquali, Gaia; Drudi, Francesco Maria

    2015-09-01

    Ganglion cysts are benign masses that originate from mucinous degeneration of the connective tissues and are quite rare when arising from the knee joint. Symptoms are often represented by pain, joint tenderness, effusion and occasional swelling with a palpable mass in the popliteal region of the knee. Percutaneous aspiration followed by a corticosteroid injection of a ganglion cyst has either a diagnostic or therapeutic meaning and its guidance through ultrasound allows the operator to make more accurate the procedure, ensuring the correct placement of the needle inside the lesion. We report our experience in the treatment of a voluminous ganglion cyst of the posterior cruciate ligament performed through the ultrasound guidance in a symptomatic young patient.

  13. Dorsal wrist ganglion: Current review of literature

    PubMed Central

    Meena, Sanjay; Gupta, Ajay

    2014-01-01

    Ganglion cyst is the most common soft tissue tumour of hand. Sixty to seventy percent of ganglion cysts are found in the dorsal aspect of the wrist. They may affect any age group; however they are more common in the twenties to forties. Its origin and pathogenesis remains enigmatic. Non-surgical treatment is unreliable with a high recurrence rates. Open surgical excision leads to unsightly scar and poor outcome. Arthroscopy excision has shown very promising result with very low recurrence rate. We reviewed the current literature available on dorsal wrist ganglion. PMID:25983472

  14. Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences

    PubMed Central

    Tanaka, Masashi; Singh Alvarado, Jonnathan; Murugan, Malavika; Mooney, Richard

    2016-01-01

    The basal ganglia (BG) promote complex sequential movements by helping to select elementary motor gestures appropriate to a given behavioral context. Indeed, Huntington’s disease (HD), which causes striatal atrophy in the BG, is characterized by hyperkinesia and chorea. How striatal cell loss alters activity in the BG and downstream motor cortical regions to cause these disorganized movements remains unknown. Here, we show that expressing the genetic mutation that causes HD in a song-related region of the songbird BG destabilizes syllable sequences and increases overall vocal activity, but leave the structure of individual syllables intact. These behavioral changes are paralleled by the selective loss of striatal neurons and reduction of inhibitory synapses on pallidal neurons that serve as the BG output. Chronic recordings in singing birds revealed disrupted temporal patterns of activity in pallidal neurons and downstream cortical neurons. Moreover, reversible inactivation of the cortical neurons rescued the disorganized vocal sequences in transfected birds. These findings shed light on a key role of temporal patterns of cortico-BG activity in the regulation of complex motor sequences and show how a genetic mutation alters cortico-BG networks to cause disorganized movements. PMID:26951661

  15. Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys☆

    PubMed Central

    Devergnas, Annaelle; Pittard, Damien; Bliwise, Donald; Wichmann, Thomas

    2014-01-01

    Parkinsonism is associated with changes in oscillatory activity patterns and increased synchronization of neurons in the basal ganglia and cortex in patients and animal models of Parkinson's disease, but the relationship between these changes and the severity of parkinsonian signs remains unclear. We examined this relationship by studying changes in local field potentials (LFPs) in the internal pallidal segment (GPi) and the subthalamic nucleus (STN), and in encephalographic signals (EEG) from the primarymotor cortex (M1) in Rhesus monkeys which were rendered progressively parkinsonian by repeated systemic injections of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Observations during wakefulness and sleep (defined by EEG and video records) were analyzed separately. The severity of parkinsonism correlated with increases in spectral power at frequencies below 15.5 Hz in M1 and GPi and reductions in spectral power at frequencies above 15.6 Hz with little change in STN. The severity of parkinsonism also correlated with increases in the coherence betweenM1 EEG and basal ganglia LFPs in the low frequency band. Levodopa treatment reduced low-frequency activity and increased high-frequency activity in all three areas, but did not affect coherence. The state of arousal also affected LFP and EEG signals in all three structures, particularly in the STN. These results suggest that parkinsonism-associated changes in alpha and low-beta band oscillatory activity can be detected early in the parkinsonian state in M1 and GPi. Interestingly, oscillations detectable in STN LFP signals (including oscillations in the beta-band) do not appear to correlate strongly with the severity of mild-to-moderate parkinsonism in these animals. Levodopa-induced changes in oscillatoryM1 EEG and basal ganglia LFP patterns do not necessarily represent a normalization of abnormalities caused by dopamine depletion. PMID:24768805

  16. Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences.

    PubMed

    Tanaka, Masashi; Singh Alvarado, Jonnathan; Murugan, Malavika; Mooney, Richard

    2016-03-22

    The basal ganglia (BG) promote complex sequential movements by helping to select elementary motor gestures appropriate to a given behavioral context. Indeed, Huntington's disease (HD), which causes striatal atrophy in the BG, is characterized by hyperkinesia and chorea. How striatal cell loss alters activity in the BG and downstream motor cortical regions to cause these disorganized movements remains unknown. Here, we show that expressing the genetic mutation that causes HD in a song-related region of the songbird BG destabilizes syllable sequences and increases overall vocal activity, but leave the structure of individual syllables intact. These behavioral changes are paralleled by the selective loss of striatal neurons and reduction of inhibitory synapses on pallidal neurons that serve as the BG output. Chronic recordings in singing birds revealed disrupted temporal patterns of activity in pallidal neurons and downstream cortical neurons. Moreover, reversible inactivation of the cortical neurons rescued the disorganized vocal sequences in transfected birds. These findings shed light on a key role of temporal patterns of cortico-BG activity in the regulation of complex motor sequences and show how a genetic mutation alters cortico-BG networks to cause disorganized movements.

  17. Molecular biology of retinal ganglion cells.

    PubMed Central

    Xiang, M; Zhou, H; Nathans, J

    1996-01-01

    Retinal ganglion cells are the output neurons that encode and transmit information from the eye to the brain. Their diverse physiologic and anatomic properties have been intensively studied and appear to account well for a number of psychophysical phenomena such as lateral inhibition and chromatic opponency. In this paper, we summarize our current view of retinal ganglion cell properties and pose a number of questions regarding underlying molecular mechanisms. As an example of one approach to understanding molecular mechanisms, we describe recent work on several POU domain transcription factors that are expressed in subsets of retinal ganglion cells and that appear to be involved in ganglion cell development. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8570601

  18. Aspergillus granuloma of the trigeminal ganglion

    PubMed Central

    Wiles, C M; Kocen, R S; Symon, L; Scaravilli, F

    1981-01-01

    A patient is described with aspergillus flavus granuloma of the trigeminal ganglion. The patient was effectively treated by surgical excision of most of the infected tissue followed by intensive chemotherapy with amphotericin B and flucytosine. Images PMID:6973615

  19. Optical properties of retinal tissue and the potential of adaptive optics to visualize retinal ganglion cells in vivo.

    PubMed

    Prasse, Martina; Rauscher, Franziska Georgia; Wiedemann, Peter; Reichenbach, Andreas; Francke, Mike

    2013-08-01

    Many efforts have been made to improve the diagnostic tools used to identify and to estimate the progress of ganglion cell and nerve fibre degeneration in glaucoma. Imaging by optical coherence tomography and measurements of the dimensions of the optic nerve head and the nerve fibre layer in central retinal areas is currently used to estimate the grade of pathological changes. The visualization and quantification of ganglion cells and nerve fibres directly in patients would dramatically improve glaucoma diagnostics. We have investigated the optical properties of cellular structures of retinal tissue in order to establish a means of visualizing and quantifying ganglion cells in the living retina without staining. We have characterized the optical properties of retinal tissue in several species including humans. Nerve fibres, blood vessels, ganglion cells and their cell processes have been visualized at high image resolution by means of the reflection mode of a confocal laser scanning microscope. The potential of adaptive optics in current imaging systems and the possibilities of imaging single ganglion cells non-invasively in patients are discussed.

  20. Biomechanics of Disc Degeneration

    PubMed Central

    Palepu, V.; Kodigudla, M.; Goel, V. K.

    2012-01-01

    Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

  1. Double Degenerate Binary Systems

    SciTech Connect

    Yakut, K.

    2011-09-21

    In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.

  2. Evaluation of the percentage of ganglion cells in the ganglion cell layer of the rodent retina

    PubMed Central

    Schlamp, Cassandra L.; Montgomery, Angela D.; Mac Nair, Caitlin E.; Schuart, Claudia; Willmer, Daniel J.

    2013-01-01

    Purpose Retinal ganglion cells comprise a percentage of the neurons actually residing in the ganglion cell layer (GCL) of the rodent retina. This estimate is useful to extrapolate ganglion cell loss in models of optic nerve disease, but the values reported in the literature are highly variable depending on the methods used to obtain them. Methods We tested three retrograde labeling methods and two immunostaining methods to calculate ganglion cell number in the mouse retina (C57BL/6). Additionally, a double-stain retrograde staining method was used to label rats (Long-Evans). The number of total neurons was estimated using a nuclear stain and selecting for nuclei that met specific criteria. Cholinergic amacrine cells were identified using transgenic mice expressing Tomato fluorescent protein. Total neurons and total ganglion cell numbers were measured in microscopic fields of 104 µm2 to determine the percentage of neurons comprising ganglion cells in each field. Results Historical estimates of the percentage of ganglion cells in the mouse GCL range from 36.1% to 67.5% depending on the method used. Experimentally, retrograde labeling methods yielded a combined estimate of 50.3% in mice. A retrograde method also yielded a value of 50.21% for rat retinas. Immunolabeling estimates were higher at 64.8%. Immunolabeling may introduce overestimates, however, with non-specific labeling effects, or ectopic expression of antigens in neurons other than ganglion cells. Conclusions Since immunolabeling methods may overestimate ganglion cell numbers, we conclude that 50%, which is consistently derived from retrograde labeling methods, is a reliable estimate of the ganglion cells in the neuronal population of the GCL. PMID:23825918

  3. Ultrasound findings of ganglions of the wrist.

    PubMed

    Päivänsalo, M; Jalovaara, P

    1991-01-01

    Fifty-one patients with a palpable swelling of a wrist or finger of suspected ganglion origin were examined by ultrasound (US). Forty-five were operated on, and a ganglion was found in 35. The ganglions took the form of cysts 0.4-4 cm in diameter (mean 1.4 cm) with a projection into the joint or tendon in 19 cases. Two patients had multiple ganglia, and two a wrist lipoma, one echo-rich and the other echo-poor with a thick wall. One patient had a giant cell tumour of the tendon sheath which was moderately echogenic in appearance, one had carpal tunnel syndrome and a ganglion-like finding at US, one had tenosynovitis and negative US and one had a prominent tendon due to postoperative sequelae, with US showing a longish echo-poor lesion. Two had hypertrophied muscle forming a long echo-poor structure, one had an exostosis and one had no abnormality in the wrist at operation. Our experiences suggest that ultrasound is useful in many cases with impression of a ganglion at palpation showing multiplicity of a lesion or for assisting in differential diagnosis, although a physical examination is mostly sufficient for diagnostic purposes. PMID:1756743

  4. Chlorogenic acid and coffee prevent hypoxia-induced retinal degeneration.

    PubMed

    Jang, Holim; Ahn, Hong Ryul; Jo, Hyoung; Kim, Kyung-A; Lee, Eun Ha; Lee, Ki Won; Jung, Sang Hoon; Lee, Chang Y

    2014-01-01

    This study explored whether chlorogenic acid (CGA) and coffee have protective effects against retinal degeneration. Under hypoxic conditions, the viability of transformed retinal ganglion (RGC-5) cells was significantly reduced by treatment with the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP). However, pretreatment with CGA attenuated cell death in a concentration-dependent manner. In addition, CGA prevented the up-regulation of apoptotic proteins such as Bad and cleaved caspase-3. Similar beneficial effects of both CGA and coffee extracts were observed in mice that had undergone an optic nerve crush (ONC) procedure. CGA and coffee extract reduced cell death by preventing the down-regulation of Thy-1. Our in vitro and in vivo studies demonstrated that coffee and its major component, CGA, significantly reduce apoptosis of retinal cells induced by hypoxia and NO, and that coffee consumption may help in preventing retinal degeneration. PMID:24295042

  5. Stem Cells, Retinal Ganglion Cells, and Glaucoma

    PubMed Central

    Sluch, Valentin M.; Zack, Donald J.

    2015-01-01

    Retinal ganglion cells represent an essential neuronal cell type for vision. These cells receive inputs from light-sensing photoreceptors via retinal interneurons and then relay these signals to the brain for further processing. Retinal ganglion cell diseases that result in cell death, e.g. glaucoma, often lead to permanent damage since mammalian nerves do not regenerate. Stem cell differentiation can generate cells needed for replacement or can be used to generate cells capable of secreting protective factors to promote survival. In addition, stem cell-derived cells can be used in drug screening research. Here, we discuss the current state of stem cell research potential for interference in glaucoma and other optic nerve diseases with a focus on stem cell differentiation to retinal ganglion cells. PMID:24732765

  6. Block of gap junctions eliminates aberrant activity and restores light responses during retinal degeneration.

    PubMed

    Toychiev, Abduqodir H; Ivanova, Elena; Yee, Christopher W; Sagdullaev, Botir T

    2013-08-28

    Retinal degeneration leads to progressive photoreceptor cell death, resulting in vision loss. Subsequently, inner retinal neurons develop aberrant synaptic activity, compounding visual impairment. In retinal ganglion cells, light responses driven by surviving photoreceptors are obscured by elevated levels of aberrant spiking activity. Here, we demonstrate in rd10 mice that targeting disruptive neuronal circuitry with a gap junction antagonist can significantly reduce excessive spiking. This treatment increases the sensitivity of the degenerated retina to light stimuli driven by residual photoreceptors. Additionally, this enhances signal transmission from inner retinal neurons to ganglion cells, potentially allowing the retinal network to preserve the fidelity of signals either from prosthetic electronic devices, or from cells optogenetically modified to transduce light. Thus, targeting maladaptive changes to the retina allows for treatments to use existing neuronal tissue to restore light sensitivity, and to augment existing strategies to replace lost photoreceptors. PMID:23986234

  7. Block of Gap Junctions Eliminates Aberrant Activity and Restores Light Responses during Retinal Degeneration

    PubMed Central

    Toychiev, Abduqodir H.; Ivanova, Elena; Yee, Christopher W.

    2013-01-01

    Retinal degeneration leads to progressive photoreceptor cell death, resulting in vision loss. Subsequently, inner retinal neurons develop aberrant synaptic activity, compounding visual impairment. In retinal ganglion cells, light responses driven by surviving photoreceptors are obscured by elevated levels of aberrant spiking activity. Here, we demonstrate in rd10 mice that targeting disruptive neuronal circuitry with a gap junction antagonist can significantly reduce excessive spiking. This treatment increases the sensitivity of the degenerated retina to light stimuli driven by residual photoreceptors. Additionally, this enhances signal transmission from inner retinal neurons to ganglion cells, potentially allowing the retinal network to preserve the fidelity of signals either from prosthetic electronic devices, or from cells optogenetically modified to transduce light. Thus, targeting maladaptive changes to the retina allows for treatments to use existing neuronal tissue to restore light sensitivity, and to augment existing strategies to replace lost photoreceptors. PMID:23986234

  8. Degenerate density perturbation theory

    NASA Astrophysics Data System (ADS)

    Palenik, Mark C.; Dunlap, Brett I.

    2016-09-01

    Fractional occupation numbers can be used in density functional theory to create a symmetric Kohn-Sham potential, resulting in orbitals with degenerate eigenvalues. We develop the corresponding perturbation theory and apply it to a system of Nd degenerate electrons in a harmonic oscillator potential. The order-by-order expansions of both the fractional occupation numbers and unitary transformations within the degenerate subspace are determined by the requirement that a differentiable map exists connecting the initial and perturbed states. Using the X α exchange-correlation (XC) functional, we find an analytic solution for the first-order density and first- through third-order energies as a function of α , with and without a self-interaction correction. The fact that the XC Hessian is not positive definite plays an important role in the behavior of the occupation numbers.

  9. Amacrine cells in the ganglion cell layer of the cat retina.

    PubMed

    Wässle, H; Chun, M H; Müller, F

    1987-11-15

    Following transection of the optic nerve, ganglion cells in the cat retina undergo retrograde degeneration. However, many small profiles (less than or equal to 10 micron) survive in the ganglion cell layer. Previously considered to be neuroglia, there is now substantial evidence that they are displaced amacrine cells. Their density increases from approximately 1,000 cells/mm2 in peripheral retina to 7,000 cells/mm2 in the central area. Their total number was found to be 850,000, which is five times the number of ganglion cells and also five times the number of astrocytes. Uptake of 3H-muscimol followed by autoradiography labelled 75% of the displaced amacrine cells; hence, the majority seem to be GABAergic. Immunocytochemistry with an antibody directed against choline-acetyl-transferase labelled approximately 10% of the displaced amacrines in the peripheral retina and 17% in the central area. Uptake of serotonin (5-HT) followed by immunocytochemistry was found in 25-30% of displaced amacrines. NADPH diaphorase histochemistry labelled approximately 5% of displaced amacrine cells. The sum of the various percentages make colocalization likely. Intracellular injection of Lucifer Yellow under microscopic control revealed that displaced amacrine cells constitute several morphological types. PMID:3693612

  10. Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion Neurons In Vitro

    PubMed Central

    Fu, Yong; Ding, Dalian; Jiang, Haiyan; Salvi, Richard

    2013-01-01

    Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochlea in vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabain in vivo varied among mammalian species. Little is known about the ototoxic effects in vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 μM for different time to elucidate the ototoxic effects of ouabain in vitro and to provide insights that could explain the comparative ototoxic effects of ouabain in vivo. Degeneration of cochlear hair cells and spiral ganglion neurons was evaluated by hair-cell staining and neurofilament labeling, respectively. Annexin V staining was used to detect apoptotic cells. A quantitative RT-PCR apoptosis-focused gene array determined changes in apoptosis-related genes. The results showed that ouabain-induced damage in vitro was dose and time dependent. 500 μM ouabain and 1000 μM ouabain were destructively traumatic to both spiral ganglion neurons and cochlear hair cells in an apoptotic signal-dependent pathway. The major apoptotic pathways in ouabain-induced spiral ganglion neuron apoptosis culminated in the stimulation of the p53 pathway and triggering of apoptosis by a network of proapoptotic signaling pathways. PMID:24228256

  11. Stratification of alpha ganglion cells and ON/OFF directionally selective ganglion cells in the rabbit retina

    PubMed Central

    ZHANG, JIAN; LI, WEI; HOSHI, HIDEO; MILLS, STEPHEN L.; MASSEY, STEPHEN C.

    2007-01-01

    The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF α ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF α ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, and co-fasciculate with the cholinergic matrix of starburst amacrine cells. However, neither ON or OFF α ganglion cells have more than a chance association with the cholinergic matrix. Z-axis reconstruction showed that OFF α ganglion cells stratify just below the cholinergic band in sublamina a while ON α ganglion cells stratify just below cholinergic b. The latter is at the same level as the terminals of calbindin bipolar cells. Thus, the calbindin bipolar cell appears to be a prime candidate to provide the bipolar cell input to ON α ganglion cells in the rabbit retina. We conclude that the precise level of stratification is correlated with the strength of cholinergic input. Alpha ganglion cells receive a weak cholinergic input and they are narrowly stratified just below the cholinergic bands. PMID:16212709

  12. Microarray analysis of gene expression in adult retinal ganglion cells.

    PubMed

    Ivanov, Dmitry; Dvoriantchikova, Galina; Nathanson, Lubov; McKinnon, Stuart J; Shestopalov, Valery I

    2006-01-01

    Retinal ganglion cells (RGCs) transfer visual information to the brain and are known to be susceptible to selective degeneration in various neuropathies such as glaucoma. This selective vulnerability suggests that these highly specialized neurons possess a distinct gene expression profile that becomes altered by neuropathy-associated stresses, which lead to the RGC death. In this study, to identify genes expressed predominantly in adult RGCs, a global transcriptional profile of purified primary RGCs has been compared to that of the whole retina. To avoid alterations of the original gene expression profile by cell culture conditions, we isolated RNA directly from adult RGCs purified by immunopanning without prior sub-cultivation. Genes expressed predominantly in RGCs included: Nrg1, Rgn, 14-3-3 family (Ywhah, Ywhaz, Ywhab), Nrn1, Gap43, Vsnl1, Rgs4. Some of these genes may serve as novel markers for these neurons. Our analysis revealed enrichment in genes controlling the pro-survival pathways in RGCs as compared to other retinal cells. PMID:16376886

  13. Neurotrophic effects of taurine on spiral ganglion neurons in vitro.

    PubMed

    Rak, Kristen; Völker, Johannes; Jürgens, Lukas; Scherzad, Agmal; Schendzielorz, Philipp; Radeloff, Andreas; Jablonka, Sibylle; Mlynski, Robert; Hagen, Rudolf

    2014-11-12

    Taurine is an ubiquitary expressed aminosulfonic acid known to play an important role in the development and maintenance of the nervous system. It is distributed in the inner ear, contributing toward the protection of hair cells against aminoglycoside-induced or bilirubin-induced ototoxicity. Thus, the question arises whether taurine also has an influence on the cellular integrity of the auditory neurons. To test this hypothesis, isolated cells of the spiral ganglion were cocultured with taurine or the neurotrophic factors brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) as controls. The analysis included cellular survival rate and neurite outgrowth. With application of taurine, the survival of glial cells and neurons was stimulated in a similar pattern, whereas BDNF and NT-3 only effected neuronal survival. Furthermore, administration of taurine resulted in enhanced neurite outgrowth comparable with the effect of the neurotrophic factors. These new insights on the neuromodulatory effects of taurine on auditory neurons suggest the use of this aminosulfonic acid to reduce the degeneration of auditory neurons in sensorineural hearing loss. Consecutively, a new therapeutical approach for the therapy of hearing impairment could be discussed. PMID:25202928

  14. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  15. Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift.

    PubMed

    Lin, Harrison W; Furman, Adam C; Kujawa, Sharon G; Liberman, M Charles

    2011-10-01

    Recent work in mouse showed that acoustic overexposure can produce a rapid and irreversible loss of cochlear nerve peripheral terminals on inner hair cells (IHCs) and a slow degeneration of spiral ganglion cells, despite full recovery of cochlear thresholds and no loss of inner or outer hair cells (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). This contrasts with earlier ultrastructural work in guinea pig suggesting that acute noise-induced neural degeneration is followed by full regeneration of cochlear nerve terminals in the IHC area (Puel et al., Neuroreport 9:2109-2114, 1998; Pujol and Puel, Ann N Y Acad Sci 884:249-254, 1999). Here, we show that the same patterns of primary neural degeneration reported for mouse are also seen in the noise-exposed guinea pig, when IHC synapses and cochlear nerve terminals are counted 1 week post-exposure in confocal images from immunostained whole mounts and that the same slow degeneration of spiral ganglion cells occurs despite no loss of IHCs and apparent recovery of cochlear thresholds. The data cast doubt on prior claims that there is significant neural regeneration and synaptogenesis in the adult cochlea and suggest that denervation of the inner hair cell is an important sequela of "reversible" noise-induced hearing loss, which likely applies to the human ear as well. PMID:21688060

  16. Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift.

    PubMed

    Lin, Harrison W; Furman, Adam C; Kujawa, Sharon G; Liberman, M Charles

    2011-10-01

    Recent work in mouse showed that acoustic overexposure can produce a rapid and irreversible loss of cochlear nerve peripheral terminals on inner hair cells (IHCs) and a slow degeneration of spiral ganglion cells, despite full recovery of cochlear thresholds and no loss of inner or outer hair cells (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). This contrasts with earlier ultrastructural work in guinea pig suggesting that acute noise-induced neural degeneration is followed by full regeneration of cochlear nerve terminals in the IHC area (Puel et al., Neuroreport 9:2109-2114, 1998; Pujol and Puel, Ann N Y Acad Sci 884:249-254, 1999). Here, we show that the same patterns of primary neural degeneration reported for mouse are also seen in the noise-exposed guinea pig, when IHC synapses and cochlear nerve terminals are counted 1 week post-exposure in confocal images from immunostained whole mounts and that the same slow degeneration of spiral ganglion cells occurs despite no loss of IHCs and apparent recovery of cochlear thresholds. The data cast doubt on prior claims that there is significant neural regeneration and synaptogenesis in the adult cochlea and suggest that denervation of the inner hair cell is an important sequela of "reversible" noise-induced hearing loss, which likely applies to the human ear as well.

  17. Learning LM Specificity for Ganglion Cells

    NASA Technical Reports Server (NTRS)

    Ahumada, Albert J.

    2015-01-01

    Unsupervised learning models have been proposed based on experience (Ahumada and Mulligan, 1990;Wachtler, Doi, Lee and Sejnowski, 2007) that allow the cortex to develop units with LM specific color opponent receptive fields like the blob cells reported by Hubel and Wiesel on the basis of visual experience. These models used ganglion cells with LM indiscriminate wiring as inputs to the learning mechanism, which was presumed to occur at the cortical level.

  18. Stellate ganglion blockade-techniques and modalities.

    PubMed

    Ghai, A; Kaushik, T; Wadhera, R; Wadhera, S

    2016-01-01

    Stellate ganglion block (SGB) is utilized in the diagnosis and management of various vascular disorders and sympathetically mediated pain in upper extremity, head and neck. The stellate ganglion lies medial to the scalene muscles, lateral to longus coli muscle, esophagus, trachea and recurrent laryngeal nerve, anterior to C7 transverse process and prevertebral fascia, superior to the subclavian artery and posterior to vertebral vessels. Consequently, inadvertent placement of the needle tip into these soft tissues and vessels occur with blind technique. Henceforth, various interventional modalities are being used for SGB, these have been reviewed in this paper. Various techniques of SGB have been described, and vary from the use of standard blind technique to the use of fluoroscopy, computerized tomography, magnetic resonance imaging, and radio nucleotide tracers. However, these techniques may not be practical in a clinical setting, insofar as they are time consuming, costly, and may involve radiation exposure. The use of fluoroscopy does not visualize the blood vessels close to the stellate ganglion. Ultrasounds are the alternative. They help in visualization of soft tissues to prevent complications and help in deposition of drug subfascially, under direct visual control. PMID:27363208

  19. Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis.

    PubMed

    Basilisco, Guido; Gebbia, Carlotta; Peracchi, Maddalena; Velio, Pietro; Conte, Dario; Bresolin, Nereo; Nobile-Orazio, Eduardo

    2005-04-01

    A 35-year-old male with an 11-year history of intestinal pseudo-obstruction associated with an idiopathic inflammatory insult of the myenteric plexus and the presence of circulating anti-Hu antibodies developed a neurological syndrome characterized by bilateral hearing loss, deteriorating balance, an unsteady gait and difficulty in estimating distances. A similar neurological syndrome has previously been described in older patients among the paraneoplasic syndromes associated with small-cell lung carcinoma and the presence of circulating anti-Hu antibodies, but never in the rare cancer-free patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction. The patient underwent a steroid treatment. No further episodes of functional intestinal obstruction were observed and, after an initial improvement, the neurological symptoms stabilized, leaving a permanent reduction in hearing function and an unsteady gait. The case shows that an idiopathic inflammatory insult of the myenteric plexus may precede (and perhaps lead to) central nervous system impairment in patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction.

  20. Two Ultracool Degenerate Companions

    NASA Astrophysics Data System (ADS)

    Farihi, J.

    2005-07-01

    In the course of an extensive survey for low mass stellar and substellar companions to nearby white dwarfs, two extrememly cool degenerate objects have been discovered. GD 392B is one of only a few known white dwarfs with Teff⪉4000 K and exhibits collision induced absorption in the near infrared tep{far04}. GD 1400B is the second known L dwarf companion to a white dwarf and a possible brown dwarf (Farihi & Christopher 2004). Interested readers should consult the references for a complete description of these two cool objects.

  1. Melanopsin retinal ganglion cell loss in Alzheimer disease

    PubMed Central

    Ross‐Cisneros, Fred N.; Koronyo, Yosef; Hannibal, Jens; Gallassi, Roberto; Cantalupo, Gaetano; Sambati, Luisa; Pan, Billy X.; Tozer, Kevin R.; Barboni, Piero; Provini, Federica; Avanzini, Pietro; Carbonelli, Michele; Pelosi, Annalisa; Chui, Helena; Liguori, Rocco; Baruzzi, Agostino; Koronyo‐Hamaoui, Maya; Sadun, Alfredo A.; Carelli, Valerio

    2015-01-01

    Objective Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction. Methods We assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls. Results We demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs. Interpretation We show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109 PMID:26505992

  2. Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss.

    PubMed

    Kujawa, Sharon G; Liberman, M Charles

    2015-12-01

    The classic view of sensorineural hearing loss (SNHL) is that the "primary" targets are hair cells, and that cochlear-nerve loss is "secondary" to hair cell degeneration. Our recent work in mouse and guinea pig has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of cochlear-nerve/hair-cell synapses. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained hidden for three reasons: 1) the spiral ganglion cells, the cochlear neural elements commonly assessed in studies of SNHL, survive for years despite loss of synaptic connection with hair cells, 2) the synaptic terminals of cochlear nerve fibers are unmyelinated and difficult to see in the light microscope, and 3) the degeneration is selective for cochlear-nerve fibers with high thresholds. Although not required for threshold detection in quiet (e.g. threshold audiometry or auditory brainstem response threshold), these high-threshold fibers are critical for hearing in noisy environments. Our research suggests that 1) primary neural degeneration is an important contributor to the perceptual handicap in SNHL, and 2) in cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from spiral ganglion neurons and re-establishment of their peripheral synapses. This article is part of a Special Issue entitled .

  3. Identification of 12/15-lipoxygenase as a regulator of axon degeneration through high-content screening.

    PubMed

    Rudhard, York; Sengupta Ghosh, Arundhati; Lippert, Beatrix; Böcker, Alexander; Pedaran, Mehdi; Krämer, Joachim; Ngu, Hai; Foreman, Oded; Liu, Yichin; Lewcock, Joseph W

    2015-02-18

    Axon degeneration is a programed process that takes place during development, in response to neuronal injury, and as a component of neurodegenerative disease pathology, yet the molecular mechanisms that drive this process remain poorly defined. In this study, we have developed a semi-automated, 384-well format axon degeneration assay in rat dorsal root ganglion (DRG) neurons using a trophic factor withdrawal paradigm. Using this setup, we have screened a library of known drugs and bioactives to identify several previously unappreciated regulators of axon degeneration, including lipoxygenases. Multiple structurally distinct lipoxygenase inhibitors as well as mouse DRG neurons lacking expression of 12/15-lipoxygenase display protection of axons in this context. Retinal ganglion cell axons from 12/15-lipoxygenase-null mice were similarly protected from degeneration following nerve crush injury. Through additional mechanistic studies, we demonstrate that lipoxygenases act cell autonomously within neurons to regulate degeneration, and are required for mitochondrial permeabilization and caspase activation in the axon. These findings suggest that these enzymes may represent an attractive target for treatment of neuropathies and provide a potential mechanism for the neuroprotection observed in various settings following lipoxygenase inhibitor treatment. PMID:25698732

  4. Concerted Signaling by Retinal Ganglion Cells

    NASA Astrophysics Data System (ADS)

    Meister, Markus; Lagnado, Leon; Baylor, Denis A.

    1995-11-01

    To analyze the rules that govern communication between eye and brain, visual responses were recorded from an intact salamander retina. Parallel observation of many retinal ganglion cells with a microelectrode array showed that nearby neurons often fired synchronously, with spike delays of less than 10 milliseconds. The frequency of such synchronous spikes exceeded the correlation expected from a shared visual stimulus up to 20-fold. Synchronous firing persisted under a variety of visual stimuli and accounted for the majority of action potentials recorded. Analysis of receptive fields showed that concerted spikes encoded information not carried by individual cells; they may represent symbols in a multineuronal code for vision.

  5. Enhanced antioxidant and protective activities on retinal ganglion cells of carotenoids-overexpressing transgenic carrot.

    PubMed

    Yoon, Kee Dong; Kang, Suk-Nam; Bae, Ji-Yeong; Lee, Haeng-Soon; Kwak, Sang-Soo; Jang, Insurk; Kim, Il-Suk; Lee, Cheol Ho; Bae, Jung Myung; Lee, Shin Woo; Ahn, Mi-Jeong

    2013-08-01

    Carotenoids are considered to act as antioxidants and protect humans from serious disorders such as skin degeneration and ageing, cardiovascular disease, certain types of cancer, and age-related diseases of the eye. In this study, these chemopreventive activities of a carotenoids-overexpressing transgenic carrot were evaluated. The results of DPPH, hydroxyl, and superoxide radical scavenging tests demonstrate that the acetone extract obtained from the taproots of the carrot plants exhibits significant antioxidant activity. A higher activity was detected in the transgenic carrot extract compared with the wild-type extract. A chemopreventive activity test for degenerative diseases of the eye revealed that pretreatment with the carrot extract reduced cell death in a retinal ganglion cell line, RGC-5 cells exposed to 1-buthionine- (R,S)-sulfoximine and L-glutamic acid.

  6. Role of CtBP2 in the Apoptosis of Retinal Ganglion Cells.

    PubMed

    Wang, Wenwen; Zhang, Guowei; Gu, Hui; Liu, Ye; Lao, Jifeng; Li, Kuifang; Guan, Huaijin

    2015-07-01

    Glaucoma damages the optic nerve and is a leading cause of irreversible blindness, and its pathogenesis remains unclear. C-terminal-binding protein 2 (CtBP2) is a transcriptional repressor which plays an important role in central nervous system injury and repair. Using the glaucoma model of DBA/2J mouse whose retina ganglion cells (RGCs) were degenerating with the process of glaucoma, we demonstrated for the first time the special relationship between CtBP2 protein and RGCs. Our research indicated that the expression of CtBP2 was gradually decreased with aging by the means of Western blotting. The CtBP2 immunoreactivity-positive cells were present in the various retinal layers, and CtBP2-positive cells were dramatically decreased in ganglion cell layer. Our research also found ectopic expression of CtBP2 can protect the apoptosis of primary mouse RGC cells induced by L-glutamate. These results suggest that CtBP2 may have a potential therapeutic effect in protecting RGC.

  7. Paraneoplastic encephalo-myelo-ganglionitis: cellular binding sites of the antineuronal antibody.

    PubMed

    Yamada, M; Inaba, A; Yamawaki, M; Ishida, K; Yokota, T; Uchihara, T; Eishi, Y; Okeda, R

    1994-01-01

    The cellular binding sites of an antineuronal antibody were characterized in an autopsy case of the paraneoplastic encephalo-myelo-ganglionitis. A 61 year-old woman developed a subacute sensorimotor polyneuropathy and, later, multiple involvement of cranial nerves, disturbance of consciousness, and generalized seizure. An autopsy revealed a small cell lung carcinoma and neuropathological changes that included disseminated encephalitis, spinal anterior horn lesions, severe loss of dorsal root ganglion neurons, and secondary degeneration and loss of the nerve fibers in the spinal posterior column and peripheral nerves. The serum IgG from the patient contained antineuronal antibody(s) including an antibody to 35- to 37-kDa neuronal antigens called anti-Hu as demonstrated in Western blot. In immunohistochemical studies, the serum IgG immunostained neurons of the brains, spinal cords, and dorsal root ganglia of humans or rats. Confocal laser-scanning microscopy revealed binding of the patient's IgG in the neuronal nuclei and cytoplasm, but not in the nucleoli. In immunoelectron microscopic studies, immunolabelling with the IgG was found diffusely in the karyoplasm, excluding nucleoli, and in the cytoplasmic matrix between the cisternae of the reticulums, Golgi apparatus, and mitochondria. Encephalo-myeloganglionitis is a clinicopathological entity frequently associated with the presence of neoplasm and antineuronal antibody, however, the role of the antibody in the pathogenesis remains to be elucidated.

  8. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    PubMed Central

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  9. Rhythmic Ganglion Cell Activity in Bleached and Blind Adult Mouse Retinas

    PubMed Central

    Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

    2014-01-01

    In retinitis pigmentosa – a degenerative disease which often leads to incurable blindness- the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor’s dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance <200 µm) reveals synchrony among homologous RGC types and a constant phase shift (∼70 msec) among heterologous cell types (ON versus OFF). The rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the

  10. Bilateral Thoracic Ganglion Cyst : A Rare Case Report

    PubMed Central

    Kazanci, Burak; Tehli, Ozkan; Guclu, Bulent

    2013-01-01

    Ganglion cysts usually arise from the tissues around the facet joints. It is usually associated with degenerative cahanges in facet joints. Bilateral thoracic ganglion cysts are very rare and there is no previous case that located in bilateral intervertebral foramen compressing the L1 nerve root associated with severe radiculopathy. We report a 53 years old woman who presented with bilateral groin pain and severe numbness. Magnetic resonance imaging revealed bilateral cystic mass in the intervertebral foramen between 12th thoracal and 1st lumbar vertebrae. The cystic lesions were removed after bilateral exposure of Th12-L1 foramens. The result of hystopathology confirmed the diagnosis as ganglion cyst. The ganglion cyst may compromise lumbar dorsal ganglion when it located in the intervertebral foramen. The surgeon should keep this rare entity in their mind for differential diagnosis. PMID:23908708

  11. Adrenal medullary ganglion neurons project into the splanchnic nerve.

    PubMed

    Dagerlind, A; Pelto-Huikko, M; Diez, M; Hökfelt, T

    1995-12-01

    Retrograde tract-tracing was used to study the projections of adrenal medullary ganglion neurons. The splanchnic nerve was cut close to the suprarenal ganglia and the retrograde tracer FluoroGold was applied at the site of nerve transection. Groups of adrenal medullary ganglion neurons exhibited FlurorGold- or Fast Blue-induced fluorescence restricted to the perikarya. Using immunohistochemistry most retrogradely labelled ganglion neurons showed immunoreactivity for neuropeptide Y. In addition, after splanchnicotomy most ganglion neurons expressed galanin and galanin message-associated peptide immunoreactivities which could not be observed in control adrenals. Taken together, the present results strongly indicate that adrenal medullary ganglion neurons project back into the splanchnic nerve perhaps representing feedback system modulating the preganglionic innervation of the adrenal gland.

  12. Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases.

    PubMed

    De Giorgio, Roberto; Barbara, Giovanni; Stanghellini, Vincenzo; De Ponti, Fabrizio; Salvioli, Beatrice; Tonini, Marcello; Velio, Pietro; Bassotti, Gabrio; Corinaldesi, Roberto

    2002-09-01

    Ganglionitis, i.e., the inflammatory neuropathy characterized by a marked lymphoplasmacellular infiltrate in the myenteric plexus, may underlie a variety of paraneoplastic, infectious, or neurological disorders, although occasional cases are idiopathic in origin. We report clinical, manometric, morphofunctional, and immunological features of three cases of idiopathic ganglionitis. All patients had megacolon and underwent surgery for repeated episodes of intestinal subocclusion. Esophageal, GI, and colonic manometry performed in one patient showed dysmotility of the whole gut. Histological examination of colonic and ileum specimens identified a prominent lymphoplasmacellular infiltrate within the myenteric plexus along with a marked decrease of a wide array of neuronal peptides/transmitters. In one patient, tissue analysis revealed progressive neuronal changes up to marked myenteric neuron damage. The inflammatory infiltrate in all patients comprised CD4+ and CD8+ T lymphocytes. Abundance of both subclasses of lymphocytes suggests that immune-mediated mechanisms were responsible for neuronal degeneration. In one patient, systemic steroid therapy brought a significant clinical improvement. The immunosuppressive approach deserves further investigation in patients with severe gut motor abnormalities attributable to idiopathic myenteric ganglionitis.

  13. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... Degeneration Diagnosis: How is AMD diagnosed? Macular Degeneration Treatment: How is AMD Treated? Macular ... macular degeneration (AMD) is a deterioration or breakdown of the eye's macula. The macula is a small area in the ...

  14. Evaluation of Fluoro-Jade C as a marker of degenerating neurons in the rat retina and optic nerve.

    PubMed

    Chidlow, Glyn; Wood, John P M; Sarvestani, Ghafar; Manavis, Jim; Casson, Robert J

    2009-03-01

    Detection of neuronal death is an essential requirement for researchers investigating retinal degeneration. Fluoro-Jade C (FJC) is a novel, fluorescent dye that has been successfully used to label degenerating neurons in the brain, but its effectiveness in the eye has not been ascertained. In the current study, we determined the efficacy of FJC for detection of neuronal degeneration in the retina and optic nerve in various paradigms of injury. N-methyl-D-aspartate (NMDA) and kainic acid-induced excitotoxicity, optic nerve transection, and bilateral occlusion of the common carotid arteries (BCCAO) were performed using standard techniques. Rats were killed at various time points and the retinas with optic nerves attached were removed for tissue processing prior to labelling for FJC, for DNA fragmentation by TUNEL or for immunohistochemical analysis. Retinas from RCS rats of different ages were also analysed. After excitotoxicity-induced injury, cell bodies and dendrites within the ganglion cell and inner plexiform layers were specifically labelled by FJC within 6h, a time point comparable to the appearance of TUNEL-positive nuclei and to reductions in mRNA levels of retinal ganglion cell-specific proteins, but in advance of alterations in some immunohistochemical markers. The number of FJC-labelled cell bodies in the retina declined over time as cell loss proceeded, although dendritic staining remained prominent. Colocalisation of FJC with TUNEL and with immunohistochemical neuronal markers was achieved. FJC was successful at identifying somato-dendritic degeneration following ischemia induced by BCCAO, but surprisingly, not after optic nerve transection. FJC visualised photoreceptor degeneration in the RCS rat, albeit less effectively than with the TUNEL assay, and was also effective for imaging and quantifying degenerating axons in the optic nerve after multiple injuries. In addition to labelling degenerating neurons, however, FJC also bound non-specifically to

  15. [Trophic disorders in ganglionitis of the superior cervical sympathetic ganglion under experimental and clinical conditions].

    PubMed

    Tebloev, I K; Karlov, V A; Gemonov, V V

    1976-01-01

    The paper is concerned with a clinical study of 9 patients where ganglionitis of the upper cervical sympathic node proceeded with an atrophy of the soft tissues in the form of facial hemiatrophy. Besides in experiments on 18 guinea pigs the authors either removed or irritated the upper cervical sympathic node and then after a certain period during 30 days performed histological and histochemical studies of the soft tissues of the animal muzzle. It was possible to mark a prevalent lesion of the skin and subcutaneous fatty tissue. In the early periods of the experiment there was a more expressed change in the metabolic reactions and less-structural disorders which developed eventually and had a secondary character due to disorders of metabolic processes. These data permit to consider that such changes take place in the faces of patients with ganglionitis of the upper cervical sympathic node.

  16. Selectivity for multiple stimulus features in retinal ganglion cells.

    PubMed

    Fairhall, Adrienne L; Burlingame, C Andrew; Narasimhan, Ramesh; Harris, Robert A; Puchalla, Jason L; Berry, Michael J

    2006-11-01

    Under normal viewing conditions, retinal ganglion cells transmit to the brain an encoded version of the visual world. The retina parcels the visual scene into an array of spatiotemporal features, and each ganglion cell conveys information about a small set of these features. We study the temporal features represented by salamander retinal ganglion cells by stimulating with dynamic spatially uniform flicker and recording responses using a multi-electrode array. While standard reverse correlation methods determine a single stimulus feature--the spike-triggered average--multiple features can be relevant to spike generation. We apply covariance analysis to determine the set of features to which each ganglion cell is sensitive. Using this approach, we found that salamander ganglion cells represent a rich vocabulary of different features of a temporally modulated visual stimulus. Individual ganglion cells were sensitive to at least two and sometimes as many as six features in the stimulus. While a fraction of the cells can be described by a filter-and-fire cascade model, many cells have feature selectivity that has not previously been reported. These reverse models were able to account for 80-100% of the information encoded by ganglion cells. PMID:16914609

  17. Neuronal cell lines as model dorsal root ganglion neurons

    PubMed Central

    Yin, Kathleen; Baillie, Gregory J

    2016-01-01

    Background Dorsal root ganglion neuron-derived immortal cell lines including ND7/23 and F-11 cells have been used extensively as in vitro model systems of native peripheral sensory neurons. However, while it is clear that some sensory neuron-specific receptors and ion channels are present in these cell lines, a systematic comparison of the molecular targets expressed by these cell lines with those expressed in intact peripheral neurons is lacking. Results In this study, we examined the expression of RNA transcripts in the human neuroblastoma-derived cell line, SH-SY5Y, and two dorsal root ganglion hybridoma cell lines, F-11 and ND7/23, using Illumina next-generation sequencing, and compared the results with native whole murine dorsal root ganglions. The gene expression profiles of these three cell lines did not resemble any specific defined dorsal root ganglion subclass. The cell lines lacked many markers for nociceptive sensory neurons, such as the Transient receptor potential V1 gene, but expressed markers for both myelinated and unmyelinated neurons. Global gene ontology analysis on whole dorsal root ganglions and cell lines showed similar enrichment of biological process terms across all samples. Conclusions This paper provides insights into the receptor repertoire expressed in common dorsal root ganglion neuron-derived cell lines compared with whole murine dorsal root ganglions, and illustrates the limits and potentials of these cell lines as tools for neuropharmacological exploration. PMID:27130590

  18. Differential Calcium Signaling Mediated by Voltage-Gated Calcium Channels in Rat Retinal Ganglion Cells and Their Unmyelinated Axons

    PubMed Central

    Sargoy, Allison; Sun, Xiaoping

    2014-01-01

    Aberrant calcium regulation has been implicated as a causative factor in the degeneration of retinal ganglion cells (RGCs) in numerous injury models of optic neuropathy. Since calcium has dual roles in maintaining homeostasis and triggering apoptotic pathways in healthy and injured cells, respectively, investigation of voltage-gated Ca channel (VGCC) regulation as a potential strategy to reduce the loss of RGCs is warranted. The accessibility and structure of the retina provide advantages for the investigation of the mechanisms of calcium signalling in both the somata of ganglion cells as well as their unmyelinated axons. The goal of the present study was to determine the distribution of VGCC subtypes in the cell bodies and axons of ganglion cells in the normal retina and to define their contribution to calcium signals in these cellular compartments. We report L-type Ca channel α1C and α1D subunit immunoreactivity in rat RGC somata and axons. The N-type Ca channel α1B subunit was in RGC somata and axons, while the P/Q-type Ca channel α1A subunit was only in the RGC somata. We patch clamped isolated ganglion cells and biophysically identified T-type Ca channels. Calcium imaging studies of RGCs in wholemounted retinas showed that selective Ca channel antagonists reduced depolarization-evoked calcium signals mediated by L-, N-, P/Q- and T-type Ca channels in the cell bodies but only by L-type Ca channels in the axons. This differential contribution of VGCC subtypes to calcium signals in RGC somata and their axons may provide insight into the development of target-specific strategies to spare the loss of RGCs and their axons following injury. PMID:24416240

  19. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia

    PubMed Central

    Ramirez, Grisela

    2016-01-01

    Abstract Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein (IKBKAP). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre (Tα1-Cre). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients.

  20. Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina.

    PubMed

    Chan, Leanne L H; Lee, Eun-Jin; Humayun, Mark S; Weiland, James D

    2011-06-01

    Electrical stimulation threshold and retinal ganglion cell density were measured in a rat model of retinal degeneration. We performed in vivo electrophysiology and morphometric analysis on normal and S334ter line 3 (RD) rats (ages 84-782 days). We stimulated the retina in anesthetized animals and recorded evoked responses in the superior colliculus. Current pulses were delivered with a platinum-iridium (Pt-Ir) electrode of 75-μm diameter positioned on the epiretinal surface. In the same animals used for electrophysiology, SMI-32 immunolabeling of the retina enabled ganglion cell counting. An increase in threshold currents positively correlated with age of RD rats. SMI-32-labeled retinal ganglion cell density negatively correlated with age of RD rats. ANOVA shows that RD postnatal day (P)100 and P300 rats have threshold and density similar to normal rats, but RD P500 and P700 rats have threshold and density statistically different from normal rats (P < 0.05). Threshold charge densities were within the safety limits of Pt for all groups and pulse configurations, except at RD P600 and RD P700, where pulses were only safe up to 1- and 0.2-ms duration, respectively. Preservation of ganglion cells may enhance the efficiency and safety of electronic retinal implants.

  1. NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

    PubMed Central

    Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey

    2016-01-01

    Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.001 PMID:27735788

  2. Spectral-Domain Optical Coherence Tomography Documentation of Transsynaptic Retinal Degeneration.

    PubMed

    Schwartz, Stephen G; Pasol, Joshua; Lam, Byron L; Flynn, Harry W

    2016-08-01

    Patients with post-geniculate neurologic disease and corresponding visual field loss may have ophthalmologic abnormalities detectable by spectral-domain optical coherence tomography (SD-OCT), presumably by transsynaptic retrograde retinal degeneration. Here, three such patients (ages 13 years through 75 years) illustrate thinning of the macula and ganglion cell complex corresponding to zones of visual field loss. Thinning of the retinal nerve fiber layer is not notable in these patients. SD-OCT may be a useful technique in diagnosing and following patients with post-geniculate neurologic disease. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:768-772.]. PMID:27548455

  3. FATTY DEGENERATION OF THE CEREBRAL CORTEX IN THE PSYCHOSES, WITH SPECIAL REFERENCE TO DEMENTIA PRÆCOX

    PubMed Central

    Cotton, Henry A.

    1915-01-01

    From the data provided by our investigations we may conclude that in all pathologic processes of the cortex which end in dementia and death, the fatty degeneration of the elements of the cortex plays a not unimportant part. The characteristic change for most of the psychoses is found in a great increase in amount of fatty deposits when compared to normal individuals of the same age. In some processes such as senile dementia and dementia præcox the fatty substance appears to fill completely the cell body, and these cells have apparently lost all their functioning power. It is not common to find the fatty deposits in the processes of the ganglion cells except in dementia præcox, and to a limited extent in senile dementia. In other cases the pathological variety of the fatty deposits in the ganglion cells is seen to be diffused over the whole ganglion cell. We were able especially to observe this in infectious psychoses, in general paralysis, and in epilepsy. The so called central neuritis assumes a peculiar attitude in that it plainly leads swiftly to an acute fatty degeneration of the ganglion cells, in which there exists an inclination of the fatty granules to flow together into large masses. Frequently the fatty degeneration of the ganglion cells appears to be connected with the sclerosis of the cells, especially when it is a matter of slowly progressing alterations of degeneration. The behavior of the glia is not wholly uniform in the various disease processes. In chronic disease processes we often find that the extent of the fatty accumulations in the ganglion cells does not correspond to an equal increase in the glia cells, while the otherwise acutely degenerative alteration in the nuclei of the glia is noticeable. In acute processes we see regularly an equal accumulation of the fat in both species of cell. The conditions of the cells in the vascular wall are wholly similar to those of the glia cells. We must therefore assume that in chronic diseases the

  4. Wilson's disease (hepatolenticular degeneration).

    PubMed

    Herron, B E

    1976-01-01

    Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism which usually affects young people. Excess copper accumulates in the tissues, primarily in the liver, brain, and cornea. This copper deposition results in a wide range of hepatic and neurological symptoms, and may produce psychiatric illness. Hepatic involvement often occurs in childhood, while neurological deficits generally are detected at a later age. The disease is inherited in an autosomal recessive fashion. Ocular findings are of particular importance because the corneal copper deposition, forming the Kayser-Fleischer ring,is the only pathognomonic sign of the disease. The structure of the ring and the presence of copper have been well established. An anterior capsular deposition of copper in the lens results in a characteristic sunflower cataract in some of these patients. Other ocular abnormalities have been described but are much less common. The pathogenesis of the disease and the basic genetic defect remain obscure. It is clear that there is excess copper in the tissues, but the mechanism of its deposition is unknown. It is in some way associated with a failure to synthesize the serum copper protein ceruloplasmin normally. Another theory suggests that an abnormal protein with a high affinity for copper may bind the metal in the tissues. The diagnosis may be suggested by the clinical manifestations and confirmed by the presence of a Kayser-Fleischer ring. In the absence of these findings biochemical determinations are necessary. The most important of these are the serum ceruloplasmin, the urinary copper, and the hepatic copper concentration on biopsy. Treatment consists in the administration of the copper chelating agent, penicillamine, and the avoidance of a high copper intake. This usually results in marked clinical improvement if irreversible tissue damage has not occurred. Maintenance therapy for life is necessary in order to continue the negative

  5. Retinal Changes in an ATP-Induced Model of Retinal Degeneration

    PubMed Central

    Aplin, Felix P.; Vessey, Kirstan A.; Luu, Chi D.; Guymer, Robyn H.; Shepherd, Robert K.; Fletcher, Erica L.

    2016-01-01

    In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 h and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration. PMID:27199678

  6. [Retinal and trabecular degeneration in glaucoma: new insights into pathogenesis and treatment].

    PubMed

    Denoyer, A; Roubeix, C; Sapienza, A; Réaux-Le Goazigo, A; Mélik-Parsadaniantz, S; Baudouin, C

    2015-04-01

    Academic and industrial research has brought new insights into the pathogenesis of glaucoma, aiming at identifying and targeting specific mechanisms to improve our current therapeutic strategy. Retinal neurodegeneration is still the main focus, whether in terms of extrinsic factors such as neurotrophin deprivation, glutamate toxicity, vascular deficiency and neuro-inflammation from glial cells, or in terms of retinal ganglion cell intrinsic sensibility to proapoptotic signals. However, glaucoma is not solely a retinal disease but also involves retinal and trabecular meshwork degeneration, extending into and/or even originating from the brain. The present review summarizes our current knowledge of key mechanisms involved in glaucoma degeneration, focusing on the direction of current research towards the future of glaucoma therapy.

  7. [Retinal and trabecular degeneration in glaucoma: new insights into pathogenesis and treatment].

    PubMed

    Denoyer, A; Roubeix, C; Sapienza, A; Réaux-Le Goazigo, A; Mélik-Parsadaniantz, S; Baudouin, C

    2015-04-01

    Academic and industrial research has brought new insights into the pathogenesis of glaucoma, aiming at identifying and targeting specific mechanisms to improve our current therapeutic strategy. Retinal neurodegeneration is still the main focus, whether in terms of extrinsic factors such as neurotrophin deprivation, glutamate toxicity, vascular deficiency and neuro-inflammation from glial cells, or in terms of retinal ganglion cell intrinsic sensibility to proapoptotic signals. However, glaucoma is not solely a retinal disease but also involves retinal and trabecular meshwork degeneration, extending into and/or even originating from the brain. The present review summarizes our current knowledge of key mechanisms involved in glaucoma degeneration, focusing on the direction of current research towards the future of glaucoma therapy. PMID:25659482

  8. T-cell-mediated ganglionitis associated with acute sensory neuronopathy.

    PubMed

    Hainfellner, J A; Kristoferitsch, W; Lassmann, H; Bernheimer, H; Neisser, A; Drlicek, M; Beer, F; Budka, H

    1996-04-01

    A 67-year-old man presented with acute painful sensory loss, areflexia, ataxia, urinary retention, and severe constipation and became unable to walk within 2 weeks. He died suddenly 5 weeks after the onset of symptoms. Autopsy revealed widespread inflammation of sensory and autonomic ganglia with immunocytochemical evidence of a CD8+ T cell-mediated cytotoxic attack against ganglion neurons. This observation suggests a novel pathogenetic mechanism of immune-mediated human ganglion cell damage comparable to mechanisms operating in polymyositis.

  9. Temporary Neurotrophin Treatment Prevents Deafness-Induced Auditory Nerve Degeneration and Preserves Function.

    PubMed

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B; Klis, Sjaak F L; Grolman, Wilko

    2015-09-01

    After substantial loss of cochlear hair cells, exogenous neurotrophins prevent degeneration of the auditory nerve. Because cochlear implantation, the current therapy for profound sensorineural hearing loss, depends on a functional nerve, application of neurotrophins is being investigated. We addressed two questions important for fundamental insight into the effects of exogenous neurotrophins on a degenerating neural system, and for translation to the clinic. First, does temporary treatment with brain-derived neurotrophic factor (BDNF) prevent nerve degeneration on the long term? Second, how does a BDNF-treated nerve respond to electrical stimulation? Deafened guinea pigs received a cochlear implant, and their cochleas were infused with BDNF for 4 weeks. Up to 8 weeks after treatment, their cochleas were analyzed histologically. Electrically evoked compound action potentials (eCAPs) were recorded using stimulation paradigms that are informative of neural survival. Spiral ganglion cell (SGC) degeneration was prevented during BDNF treatment, resulting in 1.9 times more SGCs than in deafened untreated cochleas. Importantly, SGC survival was almost complete 8 weeks after treatment cessation, when 2.6 times more SGCs were observed. In four eCAP characteristics (three involving alteration of the interphase gap of the biphasic current pulse and one involving pulse trains), we found large and statistically significant differences between normal-hearing and deaf controls. Importantly, for BDNF-treated animals, these eCAP characteristics were near normal, suggesting healthy responsiveness of BDNF-treated SGCs. In conclusion, clinically practicable short-term neurotrophin treatment is sufficient for long-term survival of SGCs, and it can restore or preserve SGC function well beyond the treatment period. Significance statement: Successful restoration of hearing in deaf subjects by means of a cochlear implant requires a healthy spiral ganglion cell population. Deafness

  10. [Application of ganglion impar block in patient with coccyx dislocation].

    PubMed

    Sağır, Ozlem; Ozaslan, Sabri; Köroğlu, Ahmet

    2011-07-01

    Sacrococcygeal dislocation is a rare injury. The ganglion impar (also called the ganglion of Walther) is a single, small solitary, sympathetic ganglion located in the retrorectal space, anterior to the sacrococcygeal joint or coccyx. It provides the nociceptive and sympathetic supply to the perineal structure. Ganglion impar blockade is not a routinely used anesthetic and analgesic procedure in clinical practice. An elective intrarectal manuel treatment was planned for a woman patient with coccyx dislocation due to falling down from a chair 5 days ago. Ganglion impar block was performed with saccrococcygeal approach using 22 gauge spinal needle along with fluoroscopy following routine monitorization. Blood pressure, heart rate, peripheral oxygen saturation and visual analog scale (VAS) were recorded before and, after block with three minute intervals. VAS value of the patient, 8 before the procedure, decreased 50% 6 minutes after block. Intrarectal manuel treatment was applied to the patient with VAS of 0 at 9th minute. Hemodynamic values were within normal limits during and after the procedure and no motor block was observed. The patient with VAS of 0 at 2nd and 6th hour after block was discharged. VAS of 0 was determined at 24th and 48th hour by phone call. In conclusion, ganglion impar block provided adequate analgesia without causing any complications during and after the intrarectal manuel treatment for the patient with coccyx dislocation. However, we believe that further clinical studies are required to establish the safety and efficiency of this technique for other procedures at perianal region.

  11. Ganglion ultrastructure in phylactolaemate Bryozoa: evidence for a neuroepithelium.

    PubMed

    Gruhl, Alexander; Bartolomaeus, Thomas

    2008-05-01

    In contrast to other Bryozoa, members of the subtaxon Phylactolaemata bear a subepithelial cerebral ganglion that resembles a hollow vesicle rather than being compact. In older studies this ganglion was said to originate by an invagination of the pharyngeal epithelium. Unfortunately, documentation for this is fragmentary. In chordates the central nervous system also arises by an invagination-like process, but this mode is uncommon among invertebrate phyla. As a first attempt to gather more data about this phenomenon, cerebral ganglia in two phylactolaemate species, Fredericella sultana and Plumatella emarginata, were examined at the ultrastructural level. In both species the ganglion bears a small central lumen. The ganglionic cells are organized in the form of a neuroepithelium. They are polarized and interconnected by adherens junctions on their apical sides and reside on a basal lamina. The nerve cell somata are directed towards the central lumen, whereas the majority of nervous processes are distributed basally. Orientation of the neuroepithelial cells can be best explained by the possibility that they develop by invagination. A comparison with potential outgroups reveals that a neuroepithelial ganglion is at least derived. Since, however, a reliable phylogenetic system of the Bryozoa is missing, a decision on whether such a ganglion is apomorphic for Bryozoa or evolved within this taxon can hardly be made.

  12. Mice with a targeted disruption of the neurotrophin receptor trkB lose their gustatory ganglion cells early but do develop taste buds.

    PubMed

    Fritzsch, B; Sarai, P A; Barbacid, M; Silos-Santiago, I

    1997-07-01

    The alleged ability of taste afferents to induce taste buds in developing animals is investigated using a mouse model with a targeted deletion of the tyrosine kinase receptor trkB for the neurotrophin BDNF. This neurotrophin was recently shown to be expressed in developing taste buds and the receptor trkB has been shown to be expressed in the developing ganglion cells that innervate the taste buds. Our data show a reduction of geniculate ganglion cells to about 5% of control animals in neonates. Degeneration of ganglion cells starts when processes reach the central target (solitary tract) but before they reach the peripheral target (taste buds). Degeneration of ganglion cells is almost completed in trkB knockout mice before taste afferents reach in control animals the developing fungiform papillae. Four days later the first taste buds can be identified in fungiform papillae of both control and trkB knockout mice in about equal number and density. Many taste buds undergo a normal maturation compared to control animals. However, the more lateral and caudal fungiform papillae grow less in size and become less conspicuous in older trkB knockout mice. No intragemmal innervation can be found in trkB knockout taste buds but a few extragemmal fibers enter the apex and end between taste had cells without forming specialized synapses. Taste buds of trkB knockout mice appear less well organized than those of control mice, but some cells show similar vesicle accumulations as control taste bud cells in their base but no synaptic contact to an afferent. These data strongly suggest that the initial-development of many fungiform papillae and taste buds is independent of the specific taste innervation. It remains to be shown why others appear to be more dependent on proper innervation. PMID:9263033

  13. The effect of deafness duration on neurotrophin gene therapy for spiral ganglion neuron protection.

    PubMed

    Wise, Andrew K; Tu, Tian; Atkinson, Patrick J; Flynn, Brianna O; Sgro, Beatrice E; Hume, Cliff; O'Leary, Stephen J; Shepherd, Robert K; Richardson, Rachael T

    2011-08-01

    A cochlear implant can restore hearing function by electrically exciting spiral ganglion neurons (SGNs) in the deaf cochlea. However, following deafness SGNs undergo progressive degeneration ultimately leading to their death. One significant cause of SGN degeneration is the loss of neurotrophic support that is normally provided by cells within the organ of Corti (OC). The administration of exogenous neurotrophins (NTs) can protect SGNs from degeneration but the effects are short-lived once the source of NTs has been exhausted. NT gene therapy, whereby cells within the cochlea are transfected with genes enabling them to produce NTs, is one strategy for providing a cellular source of NTs that may provide long-term support for SGNs. As the SGNs normally innervate sensory cells within the OC, targeting residual OC cells for gene therapy in the deaf cochlea may provide a source of NTs for SGN protection and targeted regrowth of their peripheral fibers. However, the continual degeneration of the OC over extended periods of deafness may deplete the cellular targets for NT gene therapy and hence limit the effectiveness of this method in preventing SGN loss. This study examined the effects of deafness duration on the efficacy of NT gene therapy in preventing SGN loss in guinea pigs that were systemically deafened with aminoglycosides. Adenoviral vectors containing green fluorescent protein (GFP) with or without genes for Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT3) were injected into the scala media (SM) compartment of cochleae that had been deafened for one, four or eight weeks prior to the viral injection. The results showed that viral transfection of cells within the SM was still possible even after severe degeneration of the OC. Supporting cells (pillar and Deiters' cells), cells within the stria vascularis, the spiral ligament, endosteal cells lining the scala compartments and interdental cells in the spiral limbus were transfected. However, the

  14. Polymodal Sensory Integration in Retinal Ganglion Cells.

    PubMed

    Križaj, David

    2016-01-01

    An animal's ability to perceive the external world is conditioned by its capacity to extract and encode specific features of the visual image. The output of the vertebrate retina is not a simple representation of the 2D visual map generated by photon absorptions in the photoreceptor layer. Rather, spatial, temporal, direction selectivity and color "dimensions" of the original image are distributed in the form of parallel output channels mediated by distinct retinal ganglion cell (RGC) populations. We propose that visual information transmitted to the brain includes additional, light-independent, inputs that reflect the functional states of the retina, anterior eye and the body. These may include the local ion microenvironment, glial metabolism and systemic parameters such as intraocular pressure, temperature and immune activation which act on ion channels that are intrinsic to RGCs. We particularly focus on light-independent mechanical inputs that are associated with physical impact, cell swelling and intraocular pressure as excessive mechanical stimuli lead to the counterintuitive experience of "pressure phosphenes" and/or debilitating blinding disease such as glaucoma and diabetic retinopathy. We point at recently discovered retinal mechanosensitive ion channels as examples through which molecular physiology brings together Greek phenomenology, modern neuroscience and medicine. Thus, RGC output represents a unified picture of the embodied context within which vision takes place. PMID:26427477

  15. Advances in retinal ganglion cell imaging

    PubMed Central

    Balendra, S I; Normando, E M; Bloom, P A; Cordeiro, M F

    2015-01-01

    Glaucoma is one of the leading causes of blindness worldwide and will affect 79.6 million people worldwide by 2020. It is caused by the progressive loss of retinal ganglion cells (RGCs), predominantly via apoptosis, within the retinal nerve fibre layer and the corresponding loss of axons of the optic nerve head. One of its most devastating features is its late diagnosis and the resulting irreversible visual loss that is often predictable. Current diagnostic tools require significant RGC or functional visual field loss before the threshold for detection of glaucoma may be reached. To propel the efficacy of therapeutics in glaucoma, an earlier diagnostic tool is required. Recent advances in retinal imaging, including optical coherence tomography, confocal scanning laser ophthalmoscopy, and adaptive optics, have propelled both glaucoma research and clinical diagnostics and therapeutics. However, an ideal imaging technique to diagnose and monitor glaucoma would image RGCs non-invasively with high specificity and sensitivity in vivo. It may confirm the presence of healthy RGCs, such as in transgenic models or retrograde labelling, or detect subtle changes in the number of unhealthy or apoptotic RGCs, such as detection of apoptosing retinal cells (DARC). Although many of these advances have not yet been introduced to the clinical arena, their successes in animal studies are enthralling. This review will illustrate the challenges of imaging RGCs, the main retinal imaging modalities, the in vivo techniques to augment these as specific RGC-imaging tools and their potential for translation to the glaucoma clinic. PMID:26293138

  16. Polymodal Sensory Integration in Retinal Ganglion Cells.

    PubMed

    Križaj, David

    2016-01-01

    An animal's ability to perceive the external world is conditioned by its capacity to extract and encode specific features of the visual image. The output of the vertebrate retina is not a simple representation of the 2D visual map generated by photon absorptions in the photoreceptor layer. Rather, spatial, temporal, direction selectivity and color "dimensions" of the original image are distributed in the form of parallel output channels mediated by distinct retinal ganglion cell (RGC) populations. We propose that visual information transmitted to the brain includes additional, light-independent, inputs that reflect the functional states of the retina, anterior eye and the body. These may include the local ion microenvironment, glial metabolism and systemic parameters such as intraocular pressure, temperature and immune activation which act on ion channels that are intrinsic to RGCs. We particularly focus on light-independent mechanical inputs that are associated with physical impact, cell swelling and intraocular pressure as excessive mechanical stimuli lead to the counterintuitive experience of "pressure phosphenes" and/or debilitating blinding disease such as glaucoma and diabetic retinopathy. We point at recently discovered retinal mechanosensitive ion channels as examples through which molecular physiology brings together Greek phenomenology, modern neuroscience and medicine. Thus, RGC output represents a unified picture of the embodied context within which vision takes place.

  17. Evaluating retinal ganglion cell loss and dysfunction.

    PubMed

    Mead, Ben; Tomarev, Stanislav

    2016-10-01

    Retinal ganglion cells (RGC) bear the sole responsibility of propagating visual stimuli to the brain. Their axons, which make up the optic nerve, project from the retina to the brain through the lamina cribrosa and in rodents, decussate almost entirely at the optic chiasm before synapsing at the superior colliculus. For many traumatic and degenerative ocular conditions, the dysfunction and/or loss of RGC is the primary determinant of visual loss and are the measurable endpoints in current research into experimental therapies. To actually measure these endpoints in rodent models, techniques must ascertain both the quantity of surviving RGC and their functional capacity. Quantification techniques include phenotypic markers of RGC, retrogradely transported fluorophores and morphological measurements of retinal thickness whereas functional assessments include electroretinography (flash and pattern) and visual evoked potential. The importance of the accuracy and reliability of these techniques cannot be understated, nor can the relationship between RGC death and dysfunction. The existence of up to 30 types of RGC complicates the measuring process, particularly as these may respond differently to disease and treatment. Since the above techniques may selectively identify and ignore particular subpopulations, their appropriateness as measures of RGC survival and function may be further limited. This review discusses the above techniques in the context of their subtype specificity.

  18. Genetic Networks in Mouse Retinal Ganglion Cells

    PubMed Central

    Struebing, Felix L.; Lee, Richard K.; Williams, Robert W.; Geisert, Eldon E.

    2016-01-01

    Retinal ganglion cells (RGCs) are the output neuron of the eye, transmitting visual information from the retina through the optic nerve to the brain. The importance of RGCs for vision is demonstrated in blinding diseases where RGCs are lost, such as in glaucoma or after optic nerve injury. In the present study, we hypothesize that normal RGC function is transcriptionally regulated. To test our hypothesis, we examine large retinal expression microarray datasets from recombinant inbred mouse strains in GeneNetwork and define transcriptional networks of RGCs and their subtypes. Two major and functionally distinct transcriptional networks centering around Thy1 and Tubb3 (Class III beta-tubulin) were identified. Each network is independently regulated and modulated by unique genomic loci. Meta-analysis of publically available data confirms that RGC subtypes are differentially susceptible to death, with alpha-RGCs and intrinsically photosensitive RGCs (ipRGCs) being less sensitive to cell death than other RGC subtypes in a mouse model of glaucoma. PMID:27733864

  19. Testicular degeneration in Huntington disease.

    PubMed

    Van Raamsdonk, Jeremy M; Murphy, Zoe; Selva, David M; Hamidizadeh, Reza; Pearson, Jacqueline; Petersén, Asa; Björkqvist, Maria; Muir, Cameron; Mackenzie, Ian R; Hammond, Geoffrey L; Vogl, A Wayne; Hayden, Michael R; Leavitt, Blair R

    2007-06-01

    Huntington disease (HD) is an adult onset, neurodegenerative disorder that results from CAG expansion in the HD gene. Recent work has demonstrated testicular degeneration in mouse models of HD and alterations in the hypothalamic-pituitary-gonadal (HPG) axis in HD patients. Here, we show that HD patients have specific testicular pathology with reduced numbers of germ cells and abnormal seminiferous tubule morphology. In the YAC128 mouse model, testicular degeneration develops prior to 12 months of age, but at 12 months, there is no evidence for decreased testosterone levels or loss of GnRH neurons in the hypothalamus. This suggests that testicular pathology results from a direct toxic effect of mutant huntingtin in the testis and is supported by the fact that huntingtin is highly expressed in the affected cell populations in the testis. Understanding the pathogenesis of HD in the testis may reveal common critical pathways which lead to degeneration in both the brain and testis.

  20. Disentangling the Role of Cortico-Basal Ganglia Loops in Top-Down and Bottom-Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease.

    PubMed

    Tommasi, Giorgio; Fiorio, Mirta; Yelnik, Jérôme; Krack, Paul; Sala, Francesca; Schmitt, Emmanuelle; Fraix, Valérie; Bertolasi, Laura; Le Bas, Jean-François; Ricciardi, Giuseppe Kenneth; Fiaschi, Antonio; Theeuwes, Jan; Pollak, Pierre; Chelazzi, Leonardo

    2015-06-01

    It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and frontoparietal regions. On the other hand, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson disease (PD), a neurodegenerative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top-down and bottom-up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for our study was an attentional capture task, which enabled us to tap the competition between top-down and bottom-up mechanisms of visual attention. This task was suitably combined with a choice RT and a simple RT task to isolate any specific deficit of attention from deficits in motor response selection and initiation. In the two groups of patients, we found an equivalent increase of attentional capture but also comparable delays in target selection in the absence of any salient distractor (reflecting impaired top-down mechanisms) and movement initiation compared with controls. In contrast, motor response selection processes appeared to be prolonged only in the operated patients. Our results confirm that the BG are involved in both motor and cognitive domains. Specifically, damage to the BG, as it occurs in PD, leads to a distinct deficit of top-down control of visual attention, and this can account, albeit indirectly, for the enhancement of attentional capture, reflecting weakened ability of top-down mechanisms to antagonize bottom-up control.

  1. Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

    PubMed Central

    Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

    2014-01-01

    Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

  2. PGC-1α regulation of mitochondrial degeneration in experimental diabetic neuropathy.

    PubMed

    Choi, Joungil; Chandrasekaran, Krish; Inoue, Tatsuya; Muragundla, Anjaneyulu; Russell, James W

    2014-04-01

    Mitochondrial degeneration is considered to play an important role in the development of diabetic peripheral neuropathy in humans. Mitochondrial degeneration and the corresponding protein regulation associated with the degeneration were studied in an animal model of diabetic neuropathy. PGC-1α and its-regulated transcription factors including TFAM and NRF1, which are master regulators of mitochondrial biogenesis, are significantly downregulated in streptozotocin diabetic dorsal root ganglion (DRG) neurons. Diabetic mice develop peripheral neuropathy, loss of mitochondria, decreased mitochondrial DNA content and increased protein oxidation. Importantly, this phenotype is exacerbated in PGC-1α (-/-) diabetic mice, which develop a more severe neuropathy with reduced mitochondrial DNA and a further increase in protein oxidation. PGC-1α (-/-) diabetic mice develop an increase in total cholesterol and triglycerides, and a decrease in TFAM and NRF1 protein levels. Loss of PGC-1α causes severe mitochondrial degeneration with vacuolization in DRG neurons, coupled with reduced state 3 and 4 respiration, reduced expression of oxidative stress response genes and an increase in protein oxidation. In contrast, overexpression of PGC-1α in cultured adult mouse neurons prevents oxidative stress associated with increased glucose levels. The study provides new insights into the role of PGC-1α in mitochondrial regeneration in peripheral neurons and suggests that therapeutic modulation of PGC-1α function may be an attractive approach for treatment of diabetic neuropathy.

  3. Characterization of cytochrome c as marker for retinal cell degeneration by uv/vis spectroscopic imaging

    NASA Astrophysics Data System (ADS)

    Hollmach, Julia; Schweizer, Julia; Steiner, Gerald; Knels, Lilla; Funk, Richard H. W.; Thalheim, Silko; Koch, Edmund

    2011-07-01

    Retinal diseases like age-related macular degeneration have become an important cause of visual loss depending on increasing life expectancy and lifestyle habits. Due to the fact that no satisfying treatment exists, early diagnosis and prevention are the only possibilities to stop the degeneration. The protein cytochrome c (cyt c) is a suitable marker for degeneration processes and apoptosis because it is a part of the respiratory chain and involved in the apoptotic pathway. The determination of the local distribution and oxidative state of cyt c in living cells allows the characterization of cell degeneration processes. Since cyt c exhibits characteristic absorption bands between 400 and 650 nm wavelength, uv/vis in situ spectroscopic imaging was used for its characterization in retinal ganglion cells. The large amount of data, consisting of spatial and spectral information, was processed by multivariate data analysis. The challenge consists in the identification of the molecular information of cyt c. Baseline correction, principle component analysis (PCA) and cluster analysis (CA) were performed in order to identify cyt c within the spectral dataset. The combination of PCA and CA reveals cyt c and its oxidative state. The results demonstrate that uv/vis spectroscopic imaging in conjunction with sophisticated multivariate methods is a suitable tool to characterize cyt c under in situ conditions.

  4. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  5. Frequency Responses of Rat Retinal Ganglion Cells

    PubMed Central

    Cloherty, Shaun L.; Hung, Yu-Shan; Kameneva, Tatiana; Ibbotson, Michael R.

    2016-01-01

    There are 15–20 different types of retinal ganglion cells (RGC) in the mammalian retina, each encoding different aspects of the visual scene. The mechanism by which post-synaptic signals from the retinal network generate spikes is determined by each cell’s intrinsic electrical properties. Here we investigate the frequency responses of morphologically identified rat RGCs using intracellular injection of sinusoidal current waveforms, to assess their intrinsic capabilities with minimal contributions from the retinal network. Recorded cells were classified according to their morphological characteristics (A, B, C or D-type) and their stratification (inner (i), outer (o) or bistratified) in the inner plexiform layer (IPL). Most cell types had low- or band-pass frequency responses. A2, C1 and C4o cells were band-pass with peaks of 15–30 Hz and low-pass cutoffs above 56 Hz (A2 cells) and ~42 Hz (C1 and C4o cells). A1 and C2i/o cells were low-pass with peaks of 10–15 Hz (cutoffs 19–25 Hz). Bistratified D1 and D2 cells were also low-pass with peaks of 5–10 Hz (cutoffs ~16 Hz). The least responsive cells were the B2 and C3 types (peaks: 2–5 Hz, cutoffs: 8–11 Hz). We found no difference between cells stratifying in the inner and outer IPL (i.e., ON and OFF cells) or between cells with large and small somas or dendritic fields. Intrinsic physiological properties (input resistance, spike width and sag) had little impact on frequency response at low frequencies, but account for 30–40% of response variability at frequencies >30 Hz. PMID:27341669

  6. Ataxias and Cerebellar or Spinocerebellar Degeneration

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page Synonym(s): ... Publications and Information Publicaciones en Español What are Ataxias and Cerebellar or Spinocerebellar Degeneration? Ataxia often occurs ...

  7. Expression of Aquaporin-6 in Rat Retinal Ganglion Cells.

    PubMed

    Jang, Sun Young; Lee, Eung Suk; Ohn, Young-Hoon; Park, Tae Kwann

    2016-08-01

    Several aquaporins (AQPs) have been identified to be present in the eyes, and it has been suggested that they are involved in the movement of water and small solutes. AQP6, which has low water permeability and transports mainly anions, was recently discovered in the eyes. In the present study, we investigate the localization of AQP6 in the rat retina and show that AQP6 is selectively localized to the ganglion cell layer and the outer plexiform layer. Along with the gradual decrease in retinal ganglion cells after a crushing injury of optic nerve, immunofluorescence signals of AQP6 gradually decreased. Confocal microscope images confirmed AQP6 expression in retinal ganglion cells and Müller cells in vitro. Therefore, AQP6 might participate in water and anion transport in these cells. PMID:26526333

  8. Idiopathic myenteric ganglionitis underlying intractable vomiting in a young adult.

    PubMed

    De Giorgio, R; Barbara, G; Stanghellini, V; Cogliandro, R F; Arrigoni, A; Santini, D; Ceccarelli, C; Salvioli, B; Rossini, F P; Corinaldesi, R

    2000-06-01

    Inflammatory infiltration of intestinal myenteric plexuses (i.e. myenteric ganglionitis), along with severe intestinal motor abnormalities, may accompany paraneoplastic syndromes, neurological disorders and gastrointestinal infections, although rare cases can be idiopathic. In this report, we describe the case of a patient who presented with chronic intractable vomiting and weight loss associated with idiopathic myenteric ganglionitis mainly involving the stomach. Tissue analysis showed that the inflammatory infiltrate comprised T lymphocytes (CD4+ and CD8+), and peptide immunolabelling revealed a marked decrease of substance P/tachykinin immunoreactive staining in nerve fibres and myenteric neurones. Following systemic steroid therapy, the patient's symptoms dramatically improved, and after one year of follow-up his general condition remains satisfactory. The possible mechanisms leading to symptom generation and gastric dysmotility in the context of an idiopathic myenteric ganglionitis are discussed.

  9. Retinal Ganglion Cell Atrophy in Homonymous Hemianopia due to Acquired Occipital Lesions Observed Using Cirrus High-Definition-OCT

    PubMed Central

    Yamashita, Tsutomu; Miki, Atsushi; Goto, Katsutoshi; Araki, Syunsuke; Takizawa, Go; Ieki, Yoshiaki; Kiryu, Junichi; Tabuchi, Akio; Iguchi, Yasuyuki; Kimura, Kazumi; Yagita, Yoshiki

    2016-01-01

    Purpose. To report a reduction in macular ganglion cell layer and inner plexiform layer (GCL+IPL) thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness using spectral-domain optical coherence tomography in patients with homonymous hemianopia due to posterior cerebral artery (PCA) stroke. Methods. Seven patients with PCA stroke were examined using Cirrus high-definition-OCT. The GCL+IPL thicknesses were divided into the hemianopic and unaffected sides. The relationship between the time after stroke and the GCL+IPL thicknesses in the hemianopic side was evaluated. Results. The average thicknesses of the GCL+IPL were 64.6 and 82.0 μm on the hemianopic and unaffected sides, respectively, and the measurement was significantly thinner on the former side (p = 0.018). A regression analysis revealed a negative linear relationship (R2 = 0.574, p = 0.049) between the time after stoke and the GCL+IPL thicknesses on the hemianopic side. The supratemporal and inferotemporal cpRNFL thicknesses in the eyes ipsilateral to the stroke showed a significant reduction. Conclusion. Our findings confirmed our previous observations that the degeneration of retinal ganglion cells can occur after PCA stroke. GCL+IPL thinning was demonstrated in the hemiretinae corresponding to the affected hemifields. Also, it is suggested that the retinal changes observed are progressive. PMID:27274865

  10. KR-31378, a potassium-channel opener, induces the protection of retinal ganglion cells in rat retinal ischemic models.

    PubMed

    Choi, Anho; Choi, Jun-Sub; Yoon, Yone-Jung; Kim, Kyung-A; Joo, Choun-Ki

    2009-04-01

    KR-31378 is a newly developed K(ATP)-channel opener. To investigate the ability of KR-31378 to protect retinal ganglion cells (RGC), experiments were conducted using two retinal ischemia models. Retinal ischemia was induced by transient high intraocular pressure (IOP) for acute ischemia and by three episcleral vein occlusion for chronic retinal ischemia. KR-31378 was injected intraperitoneally and administered orally in the acute and chronic ischemia models, respectively. Under the condition of chronic ischemia, RGC density in the KR-31378-treated group was statistically higher than that in the non-treated group, and IOP was reduced. In the acute retinal ischemia model, 90% of RGC were degenerated after one week in non-treated retina, but, RGC in KR-31378-treated retina were protected from ischemic damage in a dose-dependent manner and showed inhibited glial fibrillary acidic protein (GFAP) expression. Furthermore, the KR-31378 protective effect was inhibited by glibenclamide treatment in acute ischemia. These findings indicate that systemic KR-31378 treatment may protect against ischemic injury-induced ganglion cell loss in glaucoma.

  11. Retinal Ganglion Cell Atrophy in Homonymous Hemianopia due to Acquired Occipital Lesions Observed Using Cirrus High-Definition-OCT.

    PubMed

    Yamashita, Tsutomu; Miki, Atsushi; Goto, Katsutoshi; Araki, Syunsuke; Takizawa, Go; Ieki, Yoshiaki; Kiryu, Junichi; Tabuchi, Akio; Iguchi, Yasuyuki; Kimura, Kazumi; Yagita, Yoshiki

    2016-01-01

    Purpose. To report a reduction in macular ganglion cell layer and inner plexiform layer (GCL+IPL) thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness using spectral-domain optical coherence tomography in patients with homonymous hemianopia due to posterior cerebral artery (PCA) stroke. Methods. Seven patients with PCA stroke were examined using Cirrus high-definition-OCT. The GCL+IPL thicknesses were divided into the hemianopic and unaffected sides. The relationship between the time after stroke and the GCL+IPL thicknesses in the hemianopic side was evaluated. Results. The average thicknesses of the GCL+IPL were 64.6 and 82.0 μm on the hemianopic and unaffected sides, respectively, and the measurement was significantly thinner on the former side (p = 0.018). A regression analysis revealed a negative linear relationship (R (2) = 0.574, p = 0.049) between the time after stoke and the GCL+IPL thicknesses on the hemianopic side. The supratemporal and inferotemporal cpRNFL thicknesses in the eyes ipsilateral to the stroke showed a significant reduction. Conclusion. Our findings confirmed our previous observations that the degeneration of retinal ganglion cells can occur after PCA stroke. GCL+IPL thinning was demonstrated in the hemiretinae corresponding to the affected hemifields. Also, it is suggested that the retinal changes observed are progressive. PMID:27274865

  12. Retinal ganglion cell topography and spatial resolving power in penguins.

    PubMed

    Coimbra, João Paulo; Nolan, Paul M; Collin, Shaun P; Hart, Nathan S

    2012-01-01

    Penguins are a group of flightless seabirds that exhibit numerous morphological, behavioral and ecological adaptations to their amphibious lifestyle, but little is known about the topographic organization of neurons in their retinas. In this study, we used retinal wholemounts and stereological methods to estimate the total number and topographic distribution of retinal ganglion cells in addition to an anatomical estimate of spatial resolving power in two species of penguins: the little penguin, Eudyptula minor, and the king penguin, Aptenodytes patagonicus. The total number of ganglion cells per retina was approximately 1,200,000 in the little penguin and 1,110,000 in the king penguin. The topographic distribution of retinal ganglion cells in both species revealed the presence of a prominent horizontal visual streak with steeper gradients in the little penguin. The little penguin retinas showed ganglion cell density peaks of 21,867 cells/mm², affording spatial resolution in water of 17.07-17.46 cycles/degree (12.81-13.09 cycles/degree in air). In contrast, the king penguin showed a relatively lower peak density of ganglion cells of 14,222 cells/mm², but--due to its larger eye--slightly higher spatial resolution in water of 20.40 cycles/degree (15.30 cycles/degree in air). In addition, we mapped the distribution of giant ganglion cells in both penguin species using Nissl-stained wholemounts. In both species, topographic mapping of this cell type revealed the presence of an area gigantocellularis with a concentric organization of isodensity contours showing a peak in the far temporal retina of approximately 70 cells/mm² in the little penguin and 39 cells/mm² in the king penguin. Giant ganglion cell densities gradually fall towards the outermost isodensity contours revealing the presence of a vertically organized streak. In the little penguin, we confirmed our cytological characterization of giant ganglion cells using immunohistochemistry for microtubule

  13. Eosinophilic myenteric ganglionitis is associated with functional intestinal obstruction.

    PubMed

    Schäppi, M G; Smith, V V; Milla, P J; Lindley, K J

    2003-05-01

    The diagnostic features and clinical course of three children (aged 1 month to 15 years) with severe functional intestinal obstruction and inflammation of the colonic lamina propria and myenteric plexus are described. The myenteric inflammatory infiltrate was eosinophil predominant with none of the immunological characteristics of lymphocytic ganglionitis. Neurones in the myenteric ganglia expressed the potent eosinophil chemoattractant interleukin 5. None responded to dietary exclusion but all three responded symptomatically to immunosuppression/anti-inflammatory treatments. Eosinophilic ganglionitis is associated with a pseudo-obstructive syndrome which is amenable to anti-inflammatory treatment.

  14. Ganglion Cyst Associated with Triangular Fibrocartilage Complex Tear That Caused Ulnar Nerve Compression

    PubMed Central

    Cinar, Can; Tasdelen, Neslihan

    2015-01-01

    Summary: Ganglions are the most frequently seen soft-tissue tumors in the hand. Nerve compression due to ganglion cysts at the wrist is rare. We report 2 ganglion cysts arising from triangular fibrocartilage complex, one of which caused ulnar nerve compression proximal to the Guyon's canal, leading to ulnar neuropathy. Ganglion cysts seem unimportant, and many surgeons refrain from performing a general hand examination. PMID:25878929

  15. 3-acetylpyridine-induced degeneration in the adult ascidian neural complex: Reactive and regenerative changes in glia and blood cells.

    PubMed

    Medina, Bianca N S P; Santos de Abreu, Isadora; Cavalcante, Leny A; Silva, Wagner A B; da Fonseca, Rodrigo N; Allodi, Silvana; de Barros, Cintia M

    2015-08-01

    Ascidians are interesting neurobiological models because of their evolutionary position as a sister-group of vertebrates and the high regenerative capacity of their central nervous system (CNS). We investigated the degeneration and regeneration of the cerebral ganglion complex of the ascidian Styela plicata following injection of the niacinamide antagonist 3-acetylpyridine (3AP), described as targeting the CNS of several vertebrates. For the analysis and establishment of a new model in ascidians, the ganglion complex was dissected and prepared for transmission electron microscopy (TEM), routine light microscopy (LM), immunohistochemistry and Western blotting, 1 or 10 days after injection of 3AP. The siphon stimulation test (SST) was used to quantify the functional response. One day after the injection of 3AP, CNS degeneration and recruitment of a non-neural cell type to the site of injury was observed by both TEM and LM. Furthermore, weaker immunohistochemical reactions for astrocytic glial fibrillary acidic protein (GFAP) and neuronal βIII-tubulin were observed. In contrast, the expression of caspase-3, a protein involved in the apoptotic pathway, and the glycoprotein CD34, a marker for hematopoietic stem cells, increased. Ten days after the injection of 3AP, the expression of markers tended toward the original condition. The SST revealed attenuation and subsequent recovery of the reflexes from 1 to 10 days after 3AP. Therefore, we have developed a new method to study ascidian neural degeneration and regeneration, and identified the decreased expression of GFAP and recruitment of blood stem cells to the damaged ganglion as reasons for the success of neuroregeneration in ascidians.

  16. Degenerating the elliptic Schlesinger system

    NASA Astrophysics Data System (ADS)

    Aminov, G. A.; Artamonov, S. B.

    2013-01-01

    We study various ways of degenerating the Schlesinger system on the elliptic curve with R marked points. We construct a limit procedure based on an infinite shift of the elliptic curve parameter and on shifts of the marked points. We show that using this procedure allows obtaining a nonautonomous Hamiltonian system describing the Toda chain with additional spin sl(N, ℂ) degrees of freedom.

  17. Light scattering of degenerate fermions

    NASA Astrophysics Data System (ADS)

    Aubin, S.; Leblanc, L. J.; Myrskog, S.; Extavour, M. H. T.; McKay, D.; Stummer, A.; Thywissen, J. H.

    2006-05-01

    We report on progress in measuring the suppression of resonant light scattering in a gas of degenerate fermions. A gas of trapped degenerate fermions is expected to exhibit narrower optical linewidths and longer excited state lifetimes than single atoms when the Fermi energy is larger than the photon recoil energy [1-3]. In this case, the number of available states into which a scattered atom can recoil is significantly reduced due to the filling of the Fermi sea. We produce a degenerate gas of 4x10^4 ultra-cold fermionic ^40K atoms by sympathetic cooling with bosonic ^87Rb in a micro-magnetic chip trap. The atoms can then be loaded into a tight dipole trap just above the surface of the chip and probed with a near resonance laser pulse. [1] Th. Busch, J. R. Anglin, J. I. Cirac, and P. Zoller, Europhys. Lett. 44, 1 (1998). [2] B. DeMarco and D. S. Jin, Phys. Rev. A 58, R4267 (1998). [3] J. Javanainen and J. Ruostekosky, Phys. Rev. A 52, 3033 (1995). Work supported by NSERC, CFI, OIT, Research Corporation, and PRO.

  18. RP cone-rod degeneration.

    PubMed Central

    Heckenlively, J R

    1987-01-01

    A group of patients with progressive retinal degeneration and visual field loss, who meet the basic definition of RP were investigated to better define the relationship of the findings on the ERG with clinical characteristics such as visual field size, presence or absence of scotomata or pseudo-altitudinal defects on visual field, amount of night blindness; and presence or absence of macular or optic nerve changes. These studies suggest that cone-rod degeneration patients of the RP type go through the following stages; early, the ERG has a definite cone-rod pattern where the rod ERG is larger than the cone ERG while both are abnormal. As the disease advances, there is more of a reduction in the scotopic ERG such that both the rod and cone ERGs become nearly equal. As the disease further progresses the ERG becomes non-recordable on single-flash technique, but there is good residual rod function and the final rod threshold remains good until the visual field is reduced, typically less than 10 degrees with the IV-4 isopter. Finally with advanced disease the patient becomes night blind and generally becomes very difficult to distinguished from patients who have advanced rod-cone degeneration. While it may seem logical to find that visual field size correlates with various ERG parameters; this has not been as consistent a finding in patients with rod-cone degeneration in the author's experience. The analysis shows several new pieces of information about visual field changes in cone-rod degeneration; enlarged blind spots are seen earlier in cases which have recordable cone-rod patterns (group I), and pseudo-altitudinal changes are more likely to occur in autosomal recessive patients. Patients with macular lesions and central scotomata had larger amplitudes than patients with normal appearing maculae and no central scotomata. Patients with temporal optic atrophy had an earlier onset of symptoms and significant correlation with both photopic a- and b-waves and bright flash

  19. Myelin-specific Th17 cells induce severe relapsing optic neuritis with irreversible loss of retinal ganglion cells in C57BL/6 mice

    PubMed Central

    Larabee, Chelsea M.; Hu, Yang; Desai, Shruti; Georgescu, Constantin; Wren, Jonathan D.; Axtell, Robert C.

    2016-01-01

    Purpose Optic neuritis affects most patients with multiple sclerosis (MS), and current treatments are unreliable. The purpose of this study was to characterize the contribution of Th1 and Th17 cells to the development of optic neuritis. Methods Mice were passively transferred myelin-specific Th1 or Th17 cells to induce experimental autoimmune encephalomyelitis (EAE), a model of neuroautoimmunity. Visual acuity was assessed daily with optokinetic tracking, and 1, 2, and 3 weeks post-induction, optic nerves and retinas were harvested for immunohistochemical analyses. Results Passive transfer experimental autoimmune encephalomyelitis elicits acute episodes of asymmetric visual deficits and is exacerbated in Th17-EAE relative to Th1-EAE. The Th17-EAE optic nerves contained more inflammatory infiltrates and an increased neutrophil to macrophage ratio. Significant geographic degeneration of the retinal ganglion cells accompanied Th17-EAE but not Th1. Conclusions Th17-induced transfer EAE recapitulates pathologies observed in MS-associated optic neuritis, namely, monocular episodes of vision loss, optic nerve inflammation, and geographic retinal ganglion cell (RGC) degeneration. PMID:27122964

  20. Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival

    PubMed Central

    Coleman, Jonathan A.; Zhu, Xianjun; Djajadi, Hidayat R.; Molday, Laurie L.; Smith, Richard S.; Libby, Richard T.; John, Simon W. M.; Molday, Robert S.

    2014-01-01

    ABSTRACT ATP8A2 is a P4-ATPase that is highly expressed in the retina, brain, spinal cord and testes. In the retina, ATP8A2 is localized in photoreceptors where it uses ATP to transport phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the exoplasmic to the cytoplasmic leaflet of membranes. Although mutations in ATP8A2 have been reported to cause mental retardation in humans and degeneration of spinal motor neurons in mice, the role of ATP8A2 in sensory systems has not been investigated. We have analyzed the retina and cochlea of ATP8A2-deficient mice to determine the role of ATP8A2 in visual and auditory systems. ATP8A2-deficient mice have shortened photoreceptor outer segments, a reduction in photoresponses and decreased photoreceptor viability. The ultrastructure and phagocytosis of the photoreceptor outer segment appeared normal, but the PS and PE compositions were altered and the rhodopsin content was decreased. The auditory brainstem response threshold was significantly higher and degeneration of spiral ganglion cells was apparent. Our studies indicate that ATP8A2 plays a crucial role in photoreceptor and spiral ganglion cell function and survival by maintaining phospholipid composition and contributing to vesicle trafficking. PMID:24413176

  1. Gustatory neuron types in rat geniculate ganglion.

    PubMed

    Lundy, R F; Contreras, R J

    1999-12-01

    We used extracellular single-cell recording procedures to characterize the chemical and thermal sensitivity of the rat geniculate ganglion to lingual stimulation, and to examine the effects of specific ion transport antagonists on salt transduction mechanisms. Hierarchical cluster analysis of the responses from 73 single neurons to 3 salts (0.075 and 0.3 M NaCl, KCl, and NH(4) Cl), 0.5 M sucrose, 0.01 M HCl, and 0.02 M quinine HCl (QHCl) indicated 3 main groups that responded best to either sucrose, HCl, or NaCl. Eight narrowly tuned neurons were deemed sucrose-specialists and 33 broadly tuned neurons as HCl-generalists. The NaCl group contained three identifiable subclusters: 18 NaCl-specialists, 11 NaCl-generalists, and 3 QHCl-generalists. Sucrose- and NaCl-specialists responded specifically to sucrose and NaCl, respectively. All generalist neurons responded to salt, acid, and alkaloid stimuli to varying degree and order depending on neuron type. Response order was NaCl > HCl = QHCl > sucrose in NaCl-generalists, HCl > NaCl > QHCl > sucrose in HCl-generalists, and QHCl = NaCl = HCl > sucrose in QHCl-generalists. NaCl-specialists responded robustly to low and high NaCl concentrations, but weakly, if at all, to high KCl and NH(4) Cl concentrations after prolonged stimulation. HCl-generalist neurons responded to all three salts, but at twice the rate to NH(4) Cl than to NaCl and KCl. NaCl- and QHCl-generalists responded equally to the three salts. Amiloride and 5-(N,N-dimethyl)-amiloride (DMA), antagonists of Na(+) channels and Na(+)/H(+) exchangers, respectively, inhibited the responses to 0.075 M NaCl only in NaCl-specialist neurons. The K(+) channel antagonist, 4-aminopyridine (4-AP), was without a suppressive effect on salt responses, but, when applied alone in solution, it evoked a response in many HCl-generalists and one QHCl-generalist neuron so tested. Of the 39 neurons tested for their sensitivity to temperature, 23 responded to cooling and chemical

  2. Dorsal raphe nucleus projecting retinal ganglion cells: Why Y cells?

    PubMed Central

    Pickard, Gary E.; So, Kwok-Fai; Pu, Mingliang

    2015-01-01

    Retinal ganglion Y (alpha) cells are found in retinas ranging from frogs to mice to primates. The highly conserved nature of the large, fast conducting retinal Y cell is a testament to its fundamental task, although precisely what this task is remained ill-defined. The recent discovery that Y-alpha retinal ganglion cells send axon collaterals to the serotonergic dorsal raphe nucleus (DRN) in addition to the lateral geniculate nucleus (LGN), medial interlaminar nucleus (MIN), pretectum and the superior colliculus (SC) has offered new insights into the important survival tasks performed by these cells with highly branched axons. We propose that in addition to its role in visual perception, the Y-alpha retinal ganglion cell provides concurrent signals via axon collaterals to the DRN, the major source of serotonergic afferents to the forebrain, to dramatically inhibit 5-HT activity during orientation or alerting/escape responses, which dis-facilitates ongoing tonic motor activity while dis-inhibiting sensory information processing throughout the visual system. The new data provide a fresh view of these evolutionarily old retinal ganglion cells. PMID:26363667

  3. Arthroscopic Treatment of Intraosseous Ganglion Cyst of the Lunate Bone

    PubMed Central

    Cerlier, Alexandre; Gay, André-Mathieu; Levadoux, Michel

    2015-01-01

    Intraosseous ganglion cysts are rare causes of wrist pain. Surgical treatment of this pathologic condition yields good results and a low recurrence rate. The main complications are joint stiffness and vascular disturbances of the lunate bone. Wrist arthroscopy is a surgical technique that reduces the intra-articular operative area and therefore minimizes postoperative stiffness. This article describes an arthroscopic technique used for lunate intraosseous cyst resection associated with an autologous bone graft in a series of cases to prevent joint stiffness while respecting the scapholunate ligament. This study was based on a series of 4 patients, all of whom had wrist pain because of intraosseous ganglion cysts. Arthrosynovial cyst resection, ganglion curettage, and bone grafting were performed arthroscopically. Pain had totally disappeared within 2 months after the operation in 100% of patients. The average hand grip strength was estimated at 100% compared with the opposite side, and articular ranges of motion were the same on both sides in 100% of cases. No complications were reported after surgery. On the basis of these results, arthroscopic treatment of intraosseous synovial ganglion cysts seems to be more efficient and helpful in overcoming the limitations of classic open surgery in terms of complications. PMID:26697314

  4. Molecular Responses of the Spiral Ganglion to Aminoglycosides

    ERIC Educational Resources Information Center

    Balaban, Carey D.

    2005-01-01

    Aminoglycosides are toxic to both the inner ear hair cells and the ganglion cells that give rise to the eighth cranial nerve. According to recent studies, these cells have a repertoire of molecular responses to aminoglycoside exposure that engages multiple neuroprotective mechanisms. The responses appear to involve regulation of ionic homeostasis,…

  5. The outcome of ganglion clipping in hyperhidrosis and blushing.

    PubMed

    Chou, Shah-Hwa; Kao, Eing-Long; Lin, Chien-Chih; Huang, Meei-Feng

    2006-06-01

    A total of 114 patients with various sympathetic disorders underwent endoscopic sympathetic block over different thoracic ganglions by the clipping method. The advantages of this method include the recognition of the clipped level, changeability, and reversibility. However, 4.4% of patients were unilaterally clipped at the wrong level. PMID:16763754

  6. Diffuse Traumatic Axonal Injury in the Optic Nerve Does Not Elicit Retinal Ganglion Cell Loss

    PubMed Central

    Wang, Jiaqiong; Fox, Michael A.; Povlishock, John T.

    2013-01-01

    Much of the morbidity following traumatic brain injury (TBI) is associated with traumatic axonal injury (TAI). Although most TAI studies focus on corpus callosum white matter, the visual system has received increased interest. To assess visual system TAI, we developed a mouse model of optic nerve TAI. It is unknown, however, whether this TAI causes retinal ganglion cell (RGC) death. To address this issue, YFP-16 transgenic mice were subjected to mild TBI and followed from 2 to 28 days. Neither TUNEL-positive or cleaved caspase-3 immunoreactive RGCs were observed from 2 to 28 days post-TBI. Quantification of immunoreactivity of Brn3a, an RGC marker, demonstrated no RGC loss; parallel electron microscopic analysis confirmed RGC viability. Persistent RGC survival was also consistent with the finding of reorganization in the proximal axonal segments following TAI wherein microglia/macrophages remained inactive. In contrast, activated microglia/macrophages closely enveloped the distal disconnected, degenerating axonal segments at 7 to 28 days post-injury, thereby confirming that this model consistently evoked TAI followed by disconnection. Collectively, these data provide novel insight into the evolving pathobiology associated with TAI that will form a foundation for future studies exploring TAI therapy and its downstream consequences. PMID:23860030

  7. Novel High Content Screen Detects Compounds That Promote Neurite Regeneration from Cochlear Spiral Ganglion Neurons

    PubMed Central

    Whitlon, Donna S.; Grover, Mary; Dunne, Sara F.; Richter, Sonja; Luan, Chi-Hao; Richter, Claus-Peter

    2015-01-01

    The bipolar spiral ganglion neurons (SGN) carry sound information from cochlear hair cells to the brain. After noise, antibiotic or toxic insult to the cochlea, damage to SGN and/or hair cells causes hearing impairment. Damage ranges from fiber and synapse degeneration to dysfunction and loss of cells. New interventions to regenerate peripheral nerve fibers could help reestablish transfer of auditory information from surviving or regenerated hair cells or improve results from cochlear implants, but the biochemical mechanisms to target are largely unknown. Presently, no drugs exist that are FDA approved to stimulate the regeneration of SGN nerve fibers. We designed an original phenotypic assay to screen 440 compounds of the NIH Clinical Collection directly on dissociated mouse spiral ganglia. The assay detected one compound, cerivastatin, that increased the length of regenerating neurites. The effect, mimicked by other statins at different optimal concentrations, was blocked by geranylgeraniol. These results demonstrate the utility of screening small compound libraries on mixed cultures of dissociated primary ganglia. The success of this screen narrows down a moderately sized library to a single compound which can be elevated to in-depth in vivo studies, and highlights a potential new molecular pathway for targeting of hearing loss drugs. PMID:26521685

  8. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia

    PubMed Central

    Ramirez, Grisela

    2016-01-01

    Abstract Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein (IKBKAP). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre (Tα1-Cre). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients. PMID:27699209

  9. Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

    NASA Astrophysics Data System (ADS)

    Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

    2001-03-01

    Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 ± 101 compared with 1,414 ± 36; P <0.05), but not when they were immunized 48h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure

  10. Variable phenotypic expressivity in inbred retinal degeneration mouse lines: A comparative study of C3H/HeOu and FVB/N rd1 mice

    PubMed Central

    van Wyk, Michiel; Schneider, Sabine

    2015-01-01

    Purpose Recent advances in optogenetics and gene therapy have led to promising new treatment strategies for blindness caused by retinal photoreceptor loss. Preclinical studies often rely on the retinal degeneration 1 (rd1 or Pde6brd1) retinitis pigmentosa (RP) mouse model. The rd1 founder mutation is present in more than 100 actively used mouse lines. Since secondary genetic traits are well-known to modify the phenotypic progression of photoreceptor degeneration in animal models and human patients with RP, negligence of the genetic background in the rd1 mouse model is unwarranted. Moreover, the success of various potential therapies, including optogenetic gene therapy and prosthetic implants, depends on the progress of retinal degeneration, which might differ between rd1 mice. To examine the prospect of phenotypic expressivity in the rd1 mouse model, we compared the progress of retinal degeneration in two common rd1 lines, C3H/HeOu and FVB/N. Methods We followed retinal degeneration over 24 weeks in FVB/N, C3H/HeOu, and congenic Pde6b+ seeing mouse lines, using a range of experimental techniques including extracellular recordings from retinal ganglion cells, PCR quantification of cone opsin and Pde6b transcripts, in vivo flash electroretinogram (ERG), and behavioral optokinetic reflex (OKR) recordings. Results We demonstrated a substantial difference in the speed of retinal degeneration and accompanying loss of visual function between the two rd1 lines. Photoreceptor degeneration and loss of vision were faster with an earlier onset in the FVB/N mice compared to C3H/HeOu mice, whereas the performance of the Pde6b+ mice did not differ significantly in any of the tests. By postnatal week 4, the FVB/N mice expressed significantly less cone opsin and Pde6b mRNA and had neither ERG nor OKR responses. At 12 weeks of age, the retinal ganglion cells of the FVB/N mice had lost all light responses. In contrast, 4-week-old C3H/HeOu mice still had ERG and OKR responses, and we

  11. Type II cochlear ganglion cells in the chinchilla.

    PubMed

    Ruggero, M A; Santi, P A; Rich, N C

    1982-12-01

    In order to ascertain whether Type II cochlear ganglion cells project to the brain, we have studied the retrograde transport of horseradish peroxidase (HRP) from the cochlear nucleus to the spiral ganglion of the chinchilla. In this animal there exist two types of ganglion neurons, which closely correspond to those previously described in guinea pigs, cats and rats. As in the guinea pig, the majority population (Type I) consists of relatively large, myelinated neurons. The minority population (Type II, 10% of the total population) consists of small, mostly unmyelinated cells, with filamentous cytoplasm and finely grained nuclear chromatin. Type II neurons tend to be clustered toward the peripheral side of Rosenthal's canal, often in close proximity to the intraganglionic spiral bundle. By 24 h after injections of HRP into the cochlear nucleus, incubation of the cochlear ganglion in diaminobenzidine/H2O2 reveals abundant HRP label in both Type I and Type II neurons. Type II neurons, however, tend to be labelled less intensely than Type I neurons. Control experiments, consisting of spillage of HRP solution over the cochlear nucleus, were carried out to determine how much HRP might be picked up by neurons after HRP diffusion. Comparison of cochleae from injected animals and from the control animals suggests that most of the label that was found in ganglion neurons after cochlear nucleus injections represents axonally transported HRP. We conclude, at least tentatively, that Type II neurons project to the brain. The fact that less label is found in Type II neurons that in Type I neurons suggests that the former have thinner axons and/or finer terminals in the cochlear nucleus. PMID:6185462

  12. Retinal Ganglion Cell Adaptation to Small Luminance Fluctuations

    PubMed Central

    Freeman, Daniel K.; Graña, Gilberto

    2010-01-01

    To accommodate the wide input range over which the visual system operates within the narrow output range of spiking neurons, the retina adjusts its sensitivity to the mean light level so that retinal ganglion cells can faithfully signal contrast, or relative deviations from the mean luminance. Given the large operating range of the visual system, the majority of work on luminance adaptation has involved logarithmic changes in light level. We report that luminance gain controls are recruited for remarkably small fluctuations in luminance as well. Using spike recordings from the rat optic tract, we show that ganglion cell responses to a brief flash of light are modulated in amplitude by local background fluctuations as little as 15% contrast. The time scale of the gain control is rapid (<125 ms), at least for on cells. The retinal locus of adaptation precedes the ganglion cell spike generator because response gain changes of on cells were uncorrelated with firing rate. The mechanism seems to reside within the inner retinal network and not in the photoreceptors, because the adaptation profiles of on and off cells differed markedly. The response gain changes follow Weber's law, suggesting that network mechanisms of luminance adaptation described in previous work modulates retinal ganglion cell sensitivity, not just when we move between different lighting environments, but also as our eyes scan a visual scene. Finally, we show that response amplitude is uniformly reduced for flashes on a modulated background that has spatial contrast, indicating that another gain control that integrates luminance signals nonlinearly over space operates within the receptive field center of rat ganglion cells. PMID:20538771

  13. Retinal ganglion cell adaptation to small luminance fluctuations.

    PubMed

    Freeman, Daniel K; Graña, Gilberto; Passaglia, Christopher L

    2010-08-01

    To accommodate the wide input range over which the visual system operates within the narrow output range of spiking neurons, the retina adjusts its sensitivity to the mean light level so that retinal ganglion cells can faithfully signal contrast, or relative deviations from the mean luminance. Given the large operating range of the visual system, the majority of work on luminance adaptation has involved logarithmic changes in light level. We report that luminance gain controls are recruited for remarkably small fluctuations in luminance as well. Using spike recordings from the rat optic tract, we show that ganglion cell responses to a brief flash of light are modulated in amplitude by local background fluctuations as little as 15% contrast. The time scale of the gain control is rapid (<125 ms), at least for on cells. The retinal locus of adaptation precedes the ganglion cell spike generator because response gain changes of on cells were uncorrelated with firing rate. The mechanism seems to reside within the inner retinal network and not in the photoreceptors, because the adaptation profiles of on and off cells differed markedly. The response gain changes follow Weber's law, suggesting that network mechanisms of luminance adaptation described in previous work modulates retinal ganglion cell sensitivity, not just when we move between different lighting environments, but also as our eyes scan a visual scene. Finally, we show that response amplitude is uniformly reduced for flashes on a modulated background that has spatial contrast, indicating that another gain control that integrates luminance signals nonlinearly over space operates within the receptive field center of rat ganglion cells.

  14. Flexor Tendon Sheath Ganglions: Results of Surgical Excision

    PubMed Central

    Spencer, Edwin E.

    2007-01-01

    The purpose of our study was to review the clinical features and determine the results following surgical excision of a flexor tendon sheath ganglion. A retrospective analysis of 24 consecutive patients (25 ganglions) who underwent excision of a painful flexor tendon sheath ganglion by the same surgeon was performed. The patient’s medical and operative records were reviewed. Each patient was invited to return for an evaluation, which consisted of a clinical interview, completion of a questionnaire, and physical examination. Those patients that were unable to return underwent a detailed telephone interview. Sixteen patients returned for a clinical evaluation, while eight patients underwent a telephone interview. There were 15 women and nine men, with an average age of 43 years (range, 21–68 years). The dominant hand was involved in 15 patients. The long finger was most commonly involved (11 cases). The ganglion arose from the A1 pulley in 13 cases, between the A1 and A2 pulleys in three cases, and from the A2 pulley in nine cases. At an average follow-up of 18.5 months (range, 5–38 months), all of the patients were satisfied with their final result. No patient developed a recurrence and all returned to their previous functional level. There were two minor complications that resolved uneventfully; one patient experienced mild incisional tenderness, while an additional patient experienced transient digital nerve paresthesias. We conclude that surgical excision is a simple, safe, and effective method for treating a painful ganglion of the digital flexor tendon sheath. PMID:18780066

  15. AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6β-deficient Dogs.

    PubMed

    Pichard, Virginie; Provost, Nathalie; Mendes-Madeira, Alexandra; Libeau, Lyse; Hulin, Philippe; Tshilenge, Kizito-Tshitoko; Biget, Marine; Ameline, Baptiste; Deschamps, Jack-Yves; Weber, Michel; Le Meur, Guylène; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

    2016-05-01

    We previously reported that subretinal injection of AAV2/5 RK.cpde6β allowed long-term preservation of photoreceptor function and vision in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6β deficiency. The present study builds on these earlier findings to provide a detailed assessment of the long-term effects of gene therapy on the spatiotemporal pattern of retinal degeneration in rcd1 dogs treated at 20 days of age. We analyzed the density distribution of the retinal layers and of particular photoreceptor cells in 3.5-year-old treated and untreated rcd1 dogs. Whereas no rods were observed outside the bleb or in untreated eyes, gene transfer halted rod degeneration in all vector-exposed regions. Moreover, while gene therapy resulted in the preservation of cones, glial cells and both the inner nuclear and ganglion cell layers, no cells remained in vector-unexposed retinas, except in the visual streak. Finally, the retinal structure of treated 3.5-year-old rcd1 dogs was identical to that of unaffected 4-month-old rcd1 dogs, indicating near complete preservation. Our findings indicate that gene therapy arrests the degenerative process even if intervention is initiated after the onset of photoreceptor degeneration, and point to significant potential of this therapeutic approach in future clinical trials.

  16. Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc-content

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving. M

    2014-01-01

    Degeneration of the intervertebral disc is the major contributor to back/neck and radicular pain. It is characterized by an elevation in levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1 α/β, IL-6 and IL-17 secreted by the disc cells themselves; these cytokines promote matrix degradation, chemokine production and changes in cell phenotype. The resulting imbalance between catabolic and anabolic responses leads to degeneration, as well as herniation and radicular pain. Release of chemokines from degenerating discs promote infiltration and activation of T and B cells, macrophages, neutrophils, and mast cells further amplifying the inflammatory cascade. Immunocyte migration into the disc is accompanied by the appearance of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine-mediated degenerative cascade. Taken together, the enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provide new targets for treating symptomatic disc disease. PMID:24166242

  17. Genetics, Pregnancy, and Aortic Degeneration.

    PubMed

    Crawford, Jeffrey D; Hsieh, Cindy M; Schenning, Ryan C; Slater, Matthew S; Landry, Gregory J; Moneta, Gregory L; Mitchell, Erica L

    2016-01-01

    We present a case of familial thoracic aortic aneurysm and dissection (FTAAD) in a pregnant female. FTAAD is an inherited, nonsyndromic aortopathy resulting from several genetic mutations critical to aortic wall integrity have been identified. One such mutation is the myosin heavy chain gene (MYH11) which is responsible for 1-2% of all FTAAD cases. This mutation results in aortic medial degeneration, loss of elastin, and reticulin fiber fragmentation predisposing to TAAD. Aortic disease is more aggressive during pregnancy as a result of increased wall stress from hyperdynamic cardiovascular changes and estrogen-induced aortic media degeneration. Our patient was a 29-year-old G2P1 woman at 26 weeks gestation presenting with abdominal and back pain. Work-up revealed a 6.4-cm ascending aortic aneurysm with a type A dissection extending into all arch vessels, aortic coarctation at the isthmus, and a separate focal type B aortic dissection with visceral involvement. Surgical management included concomitant cesarean section with delivery of a live premature infant, tubal ligation, ascending aortic replacement with reconstruction of the arch vessels, and aortic valve resuspension. The type B dissection was managed medically without complication. This is the first reported case of aortic dissection in a patient with FTAAD/MYH11 mutation and pregnancy. This case highlights that FTAAD and pregnancy cause aortic degeneration via distinct mechanisms and that hyperdynamics of pregnancy increase aortic wall stress. Management of pregnancy associated with aortopathy requires early transfer to a tertiary center, careful investigation to identify familial aortopathy, fetal monitoring, and a multidisciplinary team approach. PMID:26381327

  18. Degeneration of a Nonrecombining Chromosome

    NASA Astrophysics Data System (ADS)

    Rice, William R.

    1994-01-01

    Comparative studies suggest that sex chromosomes begin as ordinary autosomes that happen to carry a major sex determining locus. Over evolutionary time the Y chromosome is selected to stop recombining with the X chromosome, perhaps in response to accumulation of alleles beneficial to the heterogametic but harmful to the homogametic sex. Population genetic theory predicts that a nonrecombining Y chromosome should degenerate. Here this prediction is tested by application of specific selection pressures to Drosophila melanogaster populations. Results demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity for recombination to ameliorate such decay.

  19. Mathematical glimpse on the Y chromosome degeneration

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.

    2006-04-01

    The Y chromosomes are genetically degenerate and do not recombine with their matching partners X. Non-recombination of XY pairs has been pointed out as the key factor for the degeneration of the Y chromosome. The aim here is to show that there is a mathematical asymmetry in sex chromosomes which leads to the degeneration of Y chromosomes even in the absence of XX and XY recombination. A model for sex-chromosome evolution in a stationary regime is proposed. The consequences of their asymmetry are analyzed and lead us to a couple of conclusions. First, Y chromosome degeneration shows up sqrt{2} more often than X chromosome degeneration. Second, if nature prohibits female mortalities from beeing exactly 50%, then Y chromosome degeneration is inevitable.

  20. Axon degeneration: context defines distinct pathways.

    PubMed

    Geden, Matthew J; Deshmukh, Mohanish

    2016-08-01

    Axon degeneration is an essential part of development, plasticity, and injury response and has been primarily studied in mammalian models in three contexts: 1) Axotomy-induced Wallerian degeneration, 2) Apoptosis-induced axon degeneration (axon apoptosis), and 3) Axon pruning. These three contexts dictate engagement of distinct pathways for axon degeneration. Recent advances have identified the importance of SARM1, NMNATs, NAD+ depletion, and MAPK signaling in axotomy-induced Wallerian degeneration. Interestingly, apoptosis-induced axon degeneration and axon pruning have many shared mechanisms both in signaling (e.g. DLK, JNKs, GSK3α/β) and execution (e.g. Puma, Bax, caspase-9, caspase-3). However, the specific mechanisms by which caspases are activated during apoptosis versus pruning appear distinct, with apoptosis requiring Apaf-1 but not caspase-6 while pruning requires caspase-6 but not Apaf-1. PMID:27197022

  1. Retinal ganglion cell responses to voltage and current stimulation in wild-type and rd1 mouse retinas

    NASA Astrophysics Data System (ADS)

    Goo, Yong Sook; Ye, Jang Hee; Lee, Seokyoung; Nam, Yoonkey; Ryu, Sang Baek; Kim, Kyung Hwan

    2011-06-01

    Retinal prostheses are being developed to restore vision for those with retinal diseases such as retinitis pigmentosa or age-related macular degeneration. Since neural prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. In this paper, we focused on retinal ganglion cell (RGC) responses to different stimulation parameters and compared threshold charge densities in wild-type and rd1 mice. For this purpose, we used in vitro retinal preparations of wild-type and rd1 mice. When the neural network was stimulated with voltage- and current-controlled pulses, RGCs from both wild-type and rd1 mice responded; however the temporal pattern of RGC response is very different. In wild-type RGCs, a single peak within 100 ms appears, while multiple peaks (approximately four peaks) with ~10 Hz rhythm within 400 ms appear in RGCs in the degenerated retina of rd1 mice. We find that an anodic phase-first biphasic voltage-controlled pulse is more efficient for stimulation than a biphasic current-controlled pulse based on lower threshold charge density. The threshold charge densities for activation of RGCs both with voltage- and current-controlled pulses are overall more elevated for the rd1 mouse than the wild-type mouse. Here, we propose the stimulus range for wild-type and rd1 retinas when the optimal modulation of a RGC response is possible.

  2. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients.

  3. Signaling mechanisms regulating Wallerian degeneration

    PubMed Central

    Freeman, Marc R.

    2014-01-01

    Summary Wallerian degeneration (WD) occurs after an axon is cut or crushed and entails the disintegration and clearance of the severed axon distal to the injury site. WD was initially thought to result from the passive wasting away of the distal axonal fragment, presumably because it lacked a nutrient supply from the cell body. The discovery of the slow Wallerian degeneration (Wlds) mutant mouse, in which distal severed axons survive intact for weeks rather than only 1–2 days, radically changed our thoughts on the autonomy of axon survival. Wlds taught us that under some conditions the axonal compartment can survive for weeks after axotomy without a cell body. The phenotypic and molecular characterization of Wlds and current models for Wlds molecular function are reviewed herein—the mechanism(s) by which WldS spares severed axons remains unresolved. However, recent studies inspired by Wlds have led to the identification of the first “axon death” signaling molecules whose endogenous activities promote axon destruction during WD. PMID:24907513

  4. Incomplete segregation of endorgan-specific vestibular ganglion cells in mice and rats

    NASA Technical Reports Server (NTRS)

    Maklad, A.; Fritzsch, B.

    1999-01-01

    The endorgan-specific distribution of vestibular ganglion cells was studied in neonatal and postnatal rats and mice using indocarbocyanine dye (DiI) and dextran amines for retrograde and anterograde labeling. Retrograde DiI tracing from the anterior vertical canal labeled neurons scattered throughout the whole superior vestibular ganglion, with denser labeling at the dorsal and central regions. Horizontal canal neurons were scattered along the dorsoventral axis with more clustering toward the dorsal and ventral poles of this axis. Utricular ganglion cells occupied predominantly the central region of the superior vestibular ganglion. This utricular population overlapped with both the anterior vertical and horizontal canals' ganglion cells. Posterior vertical canal neurons were clustered in the posterior part of the inferior vestibular ganglion. The saccular neurons were distributed in the two parts of the vestibular ganglion, the superior and inferior ganglia. Within the inferior ganglion, the saccular neurons were clustered in the anterior part. In the superior ganglion, the saccular neurons were widely scattered throughout the whole ganglion with more numerous neurons at the posterior half. Small and large neurons were labeled from all endorgans. Examination of the fiber trajectory within the superior division of the vestibular nerve showed no clear lamination of the fibers innervating the different endorgans. These results demonstrate an overlapping pattern between the different populations within the superior ganglion, while in the inferior ganglion, the posterior canal and saccular neurons show tighter clustering but incomplete segregation. This distribution implies that the ganglion cells are assigned for their target during development in a stochastic rather than topographical fashion.

  5. An Unusual Cause of Foot Drop: Peroneal Extraneural Ganglion Cyst

    PubMed Central

    Zumrut, Murat; Demirayak, Mehmet; Kucukapan, Ahmet

    2016-01-01

    Peripheral neuropathies caused by ganglion cysts are quite rare, especially in the lower extremities. The case of a 64-year-old male with a 2-day history of foot drop and tenderness in the region of the left fibular neck is presented. Physical examination and electromyogram findings verified peroneal nerve palsy. Ultrasonography showed cystic mass localized proximal of the peroneal muscle structures. Magnetic resonance imaging revealed a cystic-appearing mass around the fibular neck that compressed the common peroneal nerve. Surgical excision and ligation of the cyst pedicle were performed. The pathology reports confirmed the diagnosis of a ganglion cyst. The patient regained full function within two months of the surgery. Early sensory symptoms before foot drop should be considered as an indication of surgical excision to prevent delayed damage. Ligation or electrocoagulation of the cyst pedicle should be a part of surgical procedure to avoid recurrences.

  6. An Unusual Cause of Foot Drop: Peroneal Extraneural Ganglion Cyst

    PubMed Central

    Zumrut, Murat; Demirayak, Mehmet; Kucukapan, Ahmet

    2016-01-01

    Peripheral neuropathies caused by ganglion cysts are quite rare, especially in the lower extremities. The case of a 64-year-old male with a 2-day history of foot drop and tenderness in the region of the left fibular neck is presented. Physical examination and electromyogram findings verified peroneal nerve palsy. Ultrasonography showed cystic mass localized proximal of the peroneal muscle structures. Magnetic resonance imaging revealed a cystic-appearing mass around the fibular neck that compressed the common peroneal nerve. Surgical excision and ligation of the cyst pedicle were performed. The pathology reports confirmed the diagnosis of a ganglion cyst. The patient regained full function within two months of the surgery. Early sensory symptoms before foot drop should be considered as an indication of surgical excision to prevent delayed damage. Ligation or electrocoagulation of the cyst pedicle should be a part of surgical procedure to avoid recurrences. PMID:27648065

  7. The functional diversity of retinal ganglion cells in the mouse.

    PubMed

    Baden, Tom; Berens, Philipp; Franke, Katrin; Román Rosón, Miroslav; Bethge, Matthias; Euler, Thomas

    2016-01-21

    In the vertebrate visual system, all output of the retina is carried by retinal ganglion cells. Each type encodes distinct visual features in parallel for transmission to the brain. How many such 'output channels' exist and what each encodes are areas of intense debate. In the mouse, anatomical estimates range from 15 to 20 channels, and only a handful are functionally understood. By combining two-photon calcium imaging to obtain dense retinal recordings and unsupervised clustering of the resulting sample of more than 11,000 cells, here we show that the mouse retina harbours substantially more than 30 functional output channels. These include all known and several new ganglion cell types, as verified by genetic and anatomical criteria. Therefore, information channels from the mouse eye to the mouse brain are considerably more diverse than shown thus far by anatomical studies, suggesting an encoding strategy resembling that used in state-of-the-art artificial vision systems. PMID:26735013

  8. The functional diversity of retinal ganglion cells in the mouse.

    PubMed

    Baden, Tom; Berens, Philipp; Franke, Katrin; Román Rosón, Miroslav; Bethge, Matthias; Euler, Thomas

    2016-01-21

    In the vertebrate visual system, all output of the retina is carried by retinal ganglion cells. Each type encodes distinct visual features in parallel for transmission to the brain. How many such 'output channels' exist and what each encodes are areas of intense debate. In the mouse, anatomical estimates range from 15 to 20 channels, and only a handful are functionally understood. By combining two-photon calcium imaging to obtain dense retinal recordings and unsupervised clustering of the resulting sample of more than 11,000 cells, here we show that the mouse retina harbours substantially more than 30 functional output channels. These include all known and several new ganglion cell types, as verified by genetic and anatomical criteria. Therefore, information channels from the mouse eye to the mouse brain are considerably more diverse than shown thus far by anatomical studies, suggesting an encoding strategy resembling that used in state-of-the-art artificial vision systems.

  9. An Unusual Cause of Foot Drop: Peroneal Extraneural Ganglion Cyst.

    PubMed

    Zumrut, Murat; Demirayak, Mehmet; Kucukapan, Ahmet

    2016-01-01

    Peripheral neuropathies caused by ganglion cysts are quite rare, especially in the lower extremities. The case of a 64-year-old male with a 2-day history of foot drop and tenderness in the region of the left fibular neck is presented. Physical examination and electromyogram findings verified peroneal nerve palsy. Ultrasonography showed cystic mass localized proximal of the peroneal muscle structures. Magnetic resonance imaging revealed a cystic-appearing mass around the fibular neck that compressed the common peroneal nerve. Surgical excision and ligation of the cyst pedicle were performed. The pathology reports confirmed the diagnosis of a ganglion cyst. The patient regained full function within two months of the surgery. Early sensory symptoms before foot drop should be considered as an indication of surgical excision to prevent delayed damage. Ligation or electrocoagulation of the cyst pedicle should be a part of surgical procedure to avoid recurrences. PMID:27648065

  10. Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration

    PubMed Central

    Buret, L; Rebillard, G; Brun, E; Angebault, C; Pequignot, M; Lenoir, M; Do-cruzeiro, M; Tournier, E; Cornille, K; Saleur, A; Gueguen, N; Reynier, P; Amati-Bonneau, P; Barakat, A; Blanchet, C; Chinnery, P; Yu-Wai-Man, P; Kaplan, J; Roux, A-F; Van Camp, G; Wissinger, B; Boespflug-Tanguy, O; Giraudet, F; Puel, J-L; Lenaers, G; Hamel, C; Delprat, B; Delettre, C

    2016-01-01

    In vertebrates, 14-3-3 proteins form a family of seven highly conserved isoforms with chaperone activity, which bind phosphorylated substrates mostly involved in regulatory and checkpoint pathways. 14-3-3 proteins are the most abundant protein in the brain and are abundantly found in the cerebrospinal fluid in neurodegenerative diseases, suggesting a critical role in neuron physiology and death. Here we show that 14-3-3eta-deficient mice displayed auditory impairment accompanied by cochlear hair cells' degeneration. We show that 14-3-3eta is highly expressed in the outer and inner hair cells, spiral ganglion neurons of cochlea and retinal ganglion cells. Screening of YWHAH, the gene encoding the 14-3-3eta isoform, in non-syndromic and syndromic deafness, revealed seven non-synonymous variants never reported before. Among them, two were predicted to be damaging in families with syndromic deafness. In vitro, variants of YWHAH induce mild mitochondrial fragmentation and severe susceptibility to apoptosis, in agreement with a reduced capacity of mutated 14-3-3eta to bind the pro-apoptotic Bad protein. This study demonstrates that YWHAH variants can have a substantial effect on 14-3-3eta function and that 14-3-3eta could be a critical factor in the survival of outer hair cells. PMID:27275396

  11. Colocalization of HCN Channel Subunits in Rat Retinal Ganglion Cells

    PubMed Central

    Stradleigh, Tyler W.; Ogata, Genki; Partida, Gloria J.; Oi, Hanako; Greenberg, Kenneth P.; Krempely, Kalen S.; Ishida, Andrew T.

    2011-01-01

    The current-passing pore of mammalian hyperpolarization-activated, cyclic nucleotide-gated ("HCN") channels is formed by subunit isoforms denoted HCN1-4. In various brain areas, antibodies directed against multiple isoforms bind to single neurons and the current ("Ih") passed during hyperpolarizations differs from that of heterologously expressed homomeric channels. By contrast, retinal rod, cone, and bipolar cells appear to use homomeric HCN channels. Here, we assess the generality of this pattern by examining HCN1 and HCN4 immunoreactivity in rat retinal ganglion cells, measuring Ih in dissociated cells, and testing whether HCN1 and HCN4 protein coimmunoprecipitate. Nearly half of the ganglion cells in whole-mounted retinae bound antibodies against both isoforms. Consistent with colocalization and physical association, 8-bromo-cAMP shifted the voltage-sensitivity of Ih less than that of HCN4 channels and more than that of HCN1 channels, and HCN1 coimmunoprecipitated with HCN4 from membrane fraction proteins. Lastly, the immunopositive somata ranged in diameter from the smallest to the largest in rat retina, the dendrites of immunopositive cells arborized at various levels of the inner plexiform layer and over fields of different diameters, and Ih activated with similar kinetics and proportions of fast and slow components in small, medium, and large somata. These results show that different HCN subunits colocalize in single retinal ganglion cells, identify a subunit that can reconcile native Ih properties with the previously reported presence of HCN4 in these cells, and indicate that Ih is biophysically similar in morphologically diverse retinal ganglion cells and differs from Ih in rods, cones, and bipolar cells. PMID:21456027

  12. Wide-field ganglion cells in macaque retinas

    PubMed Central

    YAMADA, ELIZABETH S.; BORDT, ANDREA S.; MARSHAK, DAVID W.

    2012-01-01

    To describe the wide-field ganglion cells, they were injected intracellularly with Neurobiotin using an in vitro preparation of macaque retina and labeled with streptavidin-Cy3. The retinas were then labeled with antibodies to choline acetyltransferase and other markers to indicate the depth of the dendrites within the inner plexiform layer (IPL) and analyzed by confocal microscopy. There were eight different subtypes of narrowly unistratified cells that ramified in each of the 5 strata, S1–5, including narrow thorny, large sparse, large moderate, large dense, large radiate, narrow wavy, large very sparse, and fine very sparse. There were four types of broadly stratified cells with dendritic trees extending from S4 to S2. One type resembled the parvocellular giant cell and another the broad thorny type described previously in primates. Another broadly stratified cell was called multi-tufted based on its distinctive dendritic branching pattern. The fourth type had been described previously, but not named; we called it broad wavy. There was a bistratified type with its major arbor in S5, the same level as the blue cone bipolar cell; it resembled the large, bistratified cell with blue ON-yellow OFF responses described recently. Two wide-field ganglion cell types were classified as diffuse because they had dendrites throughout the IPL. One had many small branches and was named thorny diffuse. The second was named smooth diffuse because it had straighter dendrites that lacked these processes. Dendrites of the large moderate and multi-tufted cells cofasciculated with ON-starburst cell dendrites and were, therefore, candidates to be ON- and ON–OFF direction-selective ganglion cells, respectively. We concluded that there are at least 15 morphoplogical types of wide-field ganglion cells in macaque retinas. PMID:16212697

  13. Ganglion cyst in children: Reviewing treatment and recurrence rates

    PubMed Central

    Simon Cypel, Tatiana Karine; Mrad, Amir; Somers, Gino; Zuker, Ronald Melvin

    2011-01-01

    BACKGROUND: Pediatric hand and wrist ganglia seem to have different epidemiological characteristics than those of adults – a majority are found on the volar aspect of the hands and wrists of patients younger than 10 years of age. OBJECTIVE: To determine the epidemiology, etiological factors, clinical presentation, treatment and outcome of patients with ganglion cysts at The Hospital for Sick Children (Toronto, Ontario). METHODS: The records of the pathology department at The Hospital for Sick Children were searched for all cases of ganglion cyst operated on between January 2000 and December 2008. RESULTS: Thirty-seven patients underwent treatment for symptomatic ganglion cyst. The mean age of the patients was 9.6 years, and there were 23 females. A mobile nodule was the initial presentation of the ganglion in 64% of the cases. Pain was the most common indication for surgical removal. Only 11.4% of patients experienced previous trauma. In 70% of the cases, the diagnosis was made clinically. The most common sites of occurrence were volar wrist (25.7%), dorsal wrist (22.8%) and the volar aspect of the base of the ring finger (17.1%). Surgical excision was the treatment of choice for 94.2% of the patients with symptomatic lesions. The minimum follow-up period was 12 months. Only one patient (2.8%) presented with recurrence in the series. CONCLUSION: Although it is possible that these findings might change with longer follow-up, the present data provide information to help guide the treatment of these cysts. Complete surgical removal is a very effective treatment, with low rates of recurrence. PMID:22654533

  14. Immunologically induced neuromodulation of guinea pig nodose ganglion neurons.

    PubMed

    Undem, B J; Hubbard, W; Weinreich, D

    1993-07-01

    The influence of specific antigen challenge on the excitability of C-cells in nodose ganglia isolated from actively sensitized guinea pigs was evaluated using intracellular recording techniques. Antigen (ovalbumin) caused a significant depolarization (approximately 8 mV) of the resting membrane potential. Antigen exposure had differing effects on the membrane input impedance; decreasing it in 15 neurons, increasing it in 6 neurons, and having no effect in 8 neurons. About 20% of guinea pig nodose C-cells reveal a long-lasting after-spike hyperpolarization (AHPslow). Antigen challenge reversibly blocked the AHPslow in 4 of 18 neurons studied in 18 ganglia. About 30% of the nodose ganglion neurons display a time- and voltage-dependent inward rectification at membrane potentials more negative than -75 mV. Exposing the ganglion to the sensitizing antigen consistently blocked this response in 8 of 8 neurons. Histological assessment of toluidine blue stained cells revealed that the nodose ganglion contained approximately 100 mast cells. Exposing the ganglion to ovalbumin stimulated mast cell degranulation, as measured by a decrease in number of stained cells, and evoked the release of histamine, PGD2, and immunoreactive peptidoleukotrienes from the tissue. The results support the hypothesis that endogenous inflammatory mediators released during the immediate hypersensitivity (allergic) reactions can modulate the excitability of primary C-fiber afferents. Mechanisms underlying antigen-induced neuromodulation of these neurons include depolarization of the resting membrane potential, changes in membrane resistance, blockade of a time- and voltage-dependent anomalous rectifier, and, in some cells, blockade of the AHPslow.

  15. Gene therapy for retinal degeneration.

    PubMed

    Reichel, M B; Ali, R R; Hunt, D M; Bhattacharya, S S

    1997-01-01

    Inherited retinal degenerations are a group of diseases leading to blindness through progressive loss of vision in many patients. Although with the cloning of more and more disease genes the knowledge on the molecular genetics of these conditions and on the apoptotic pathway as the common disease mechanism is steadily increasing, there is still no cure for those affected. In recent years, new experimental treatments have evolved through the efforts of many investigators and have been explored in animal models. The rationale of the different strategies for developing a treatment based on gene replacement or rescue of the diseased neuronal tissue with growth factors will be outlined and discussed in this paper. PMID:9323717

  16. Regularized degenerate multi-solitons

    NASA Astrophysics Data System (ADS)

    Correa, Francisco; Fring, Andreas

    2016-09-01

    We report complex PT-symmetric multi-soliton solutions to the Korteweg de-Vries equation that asymptotically contain one-soliton solutions, with each of them possessing the same amount of finite real energy. We demonstrate how these solutions originate from degenerate energy solutions of the Schrödinger equation. Technically this is achieved by the application of Darboux-Crum transformations involving Jordan states with suitable regularizing shifts. Alternatively they may be constructed from a limiting process within the context Hirota's direct method or on a nonlinear superposition obtained from multiple Bäcklund transformations. The proposed procedure is completely generic and also applicable to other types of nonlinear integrable systems.

  17. Regularized degenerate multi-solitons

    NASA Astrophysics Data System (ADS)

    Correa, Francisco; Fring, Andreas

    2016-09-01

    We report complex {P}{T} -symmetric multi-soliton solutions to the Korteweg de-Vries equation that asymptotically contain one-soliton solutions, with each of them possessing the same amount of finite real energy. We demonstrate how these solutions originate from degenerate energy solutions of the Schrödinger equation. Technically this is achieved by the application of Darboux-Crum transformations involving Jordan states with suitable regularizing shifts. Alternatively they may be constructed from a limiting process within the context Hirota's direct method or on a nonlinear superposition obtained from multiple Bäcklund transformations. The proposed procedure is completely generic and also applicable to other types of nonlinear integrable systems.

  18. Degenerate doping of metallic anodes

    DOEpatents

    Friesen, Cody A; Zeller, Robert A; Johnson, Paul B; Switzer, Elise E

    2015-05-12

    Embodiments of the invention relate to an electrochemical cell comprising: (i) a fuel electrode comprising a metal fuel, (ii) a positive electrode, (iii) an ionically conductive medium, and (iv) a dopant; the electrodes being operable in a discharge mode wherein the metal fuel is oxidized at the fuel electrode and the dopant increases the conductivity of the metal fuel oxidation product. In an embodiment, the oxidation product comprises an oxide of the metal fuel which is doped degenerately. In an embodiment, the positive electrode is an air electrode that absorbs gaseous oxygen, wherein during discharge mode, oxygen is reduced at the air electrode. Embodiments of the invention also relate to methods of producing an electrode comprising a metal and a doped metal oxidation product.

  19. White Matter Consequences of Retinal Receptor and Ganglion Cell Damage

    PubMed Central

    Ogawa, Shumpei; Takemura, Hiromasa; Horiguchi, Hiroshi; Terao, Masahiko; Haji, Tomoki; Pestilli, Franco; Yeatman, Jason D.; Tsuneoka, Hiroshi; Wandell, Brian A.; Masuda, Yoichiro

    2014-01-01

    Purpose. Patients with Leber hereditary optic neuropathy (LHON) and cone-rod dystrophy (CRD) have central vision loss; but CRD damages the retinal photoreceptor layer, and LHON damages the retinal ganglion cell (RGC) layer. Using diffusion MRI, we measured how these two types of retinal damage affect the optic tract (ganglion cell axons) and optic radiation (geniculo-striate axons). Methods. Adult onset CRD (n = 5), LHON (n = 6), and healthy controls (n = 14) participated in the study. We used probabilistic fiber tractography to identify the optic tract and the optic radiation. We compared axial and radial diffusivity at many positions along the optic tract and the optic radiation. Results. In both types of patients, diffusion measures within the optic tract and the optic radiation differ from controls. The optic tract change is principally a decrease in axial diffusivity; the optic radiation change is principally an increase in radial diffusivity. Conclusions. Both photoreceptor layer (CRD) and retinal ganglion cell (LHON) retinal disease causes substantial change in the visual white matter. These changes can be measured using diffusion MRI. The diffusion changes measured in the optic tract and the optic radiation differ, suggesting that they are caused by different biological mechanisms. PMID:25257055

  20. Paracoccygeal corkscrew approach to ganglion impar injections for tailbone pain.

    PubMed

    Foye, Patrick M; Patel, Shounuck I

    2009-01-01

    A new technique for performing nerve blocks of the ganglion impar (ganglion Walther) is presented. These injections have been reported to relieve coccydynia (tailbone pain), as well as other malignant and nonmalignant pelvic pain syndromes. A variety of techniques have been previously described for blocking this sympathetic nerve ganglion, which is located in the retrorectal space just anterior to the upper coccygeal segments. Prior techniques have included approaches through the anococcygeal ligament, through the sacrococcygeal joint, and through intracoccygeal joint spaces. This article presents a new, paracoccygeal approach whereby the needle is inserted alongside the coccyx and the needle is guided through three discrete steps with a rotating or corkscrew trajectory. Compared with some of the previously published techniques, this paracoccygeal corkscrew approach has multiple potential benefits, including ease of fluoroscopic guidance using the lateral view, ability to easily use a stylet for the spinal needle, and use of a shorter, thinner needle. While no single technique works best for all patients and each technique has potential advantages and disadvantages, this new technique adds to the available options.

  1. Diet-Induced Obesity Exacerbates Auditory Degeneration via Hypoxia, Inflammation, and Apoptosis Signaling Pathways in CD/1 Mice

    PubMed Central

    Hwang, Juen-Haur; Hsu, Chuan-Jen; Yu, Wei-Hsuan; Liu, Tien-Chen; Yang, Wei-Shiung

    2013-01-01

    The aim of this study was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity (DIO) group was fed a high fat diet and the control group was fed a standard diet of 13.43 % kcal fat. The morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared between the beginning and end of the study (4 vs. 20 weeks old). The results show that the body weight, fasting plasma triglyceride concentrations, and omental fat weight were higher in the DIO group than in the control group at the end of experiment. The auditory brainstem response thresholds at high frequencies were significantly elevated in the DIO group compared to those of the control group. Histology studies showed that, compared to the control group, the DIO group had blood vessels with smaller diameters and thicker walls in the stria vascularis at the middle and basal turns of the cochlea. The cell densities in the spiral ganglion and spiral ligament at the basal turn of the cochlea were significantly lower in the DIO group. Immunohistochemical staining showed that hypoxia-induced factor 1 (HIF-1), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), caspase 3, poly(ADP-ribose) polymerase-1, and apoptosis inducing factor were all significantly more dense in the spiral ganglion and spiral ligament at the basal turn of cochlea in the DIO group. Our results suggest that diet-induced obesity exacerbates hearing degeneration via increased hypoxia, inflammatory responses, and cell loss in the spiral ganglion and spiral ligament and is associated with the activation of both caspase-dependent and -independent apoptosis signaling pathways in CD/1 mice. PMID:23637762

  2. Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes

    PubMed Central

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Saadane, Aicha; Tonade, Deoye; Samuels, Ivy; Veenstra, Alex; Palczewski, Krzysztof; Kern, Timothy S.

    2016-01-01

    Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. Methods Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. Results Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. Conclusions Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID:27548901

  3. Degenerate adiabatic perturbation theory: Foundations and applications

    NASA Astrophysics Data System (ADS)

    Rigolin, Gustavo; Ortiz, Gerardo

    2014-08-01

    We present details and expand on the framework leading to the recently introduced degenerate adiabatic perturbation theory [Phys. Rev. Lett. 104, 170406 (2010), 10.1103/PhysRevLett.104.170406], and on the formulation of the degenerate adiabatic theorem, along with its necessary and sufficient conditions [given in Phys. Rev. A 85, 062111 (2012), 10.1103/PhysRevA.85.062111]. We start with the adiabatic approximation for degenerate Hamiltonians that paves the way to a clear and rigorous statement of the associated degenerate adiabatic theorem, where the non-Abelian geometric phase (Wilczek-Zee phase) plays a central role to its quantitative formulation. We then describe the degenerate adiabatic perturbation theory, whose zeroth-order term is the degenerate adiabatic approximation, in its full generality. The parameter in the perturbative power-series expansion of the time-dependent wave function is directly associated to the inverse of the time it takes to drive the system from its initial to its final state. With the aid of the degenerate adiabatic perturbation theory we obtain rigorous necessary and sufficient conditions for the validity of the adiabatic theorem of quantum mechanics. Finally, to illustrate the power and wide scope of the methodology, we apply the framework to a degenerate Hamiltonian, whose closed-form time-dependent wave function is derived exactly, and also to other nonexactly solvable Hamiltonians whose solutions are numerically computed.

  4. Quantitative Genetic Analysis of Retinal Degeneration in the Blind Cavefish Astyanax mexicanus

    PubMed Central

    O'Quin, Kelly E.; Yoshizawa, Masato; Doshi, Pooja; Jeffery, William R.

    2013-01-01

    The retina is the light-sensitive tissue of the eye that facilitates vision. Mutations within genes affecting eye development and retinal function cause a host of degenerative visual diseases, including retinitis pigmentosa and anophthalmia/microphthalmia. The characin fish Astyanax mexicanus includes both eyed (surface fish) and eyeless (cavefish) morphs that initially develop eyes with normal retina; however, early in development, the eyes of cavefish degenerate. Since both surface and cave morphs are members of the same species, they serve as excellent evolutionary mutant models with which to identify genes causing retinal degeneration. In this study, we crossed the eyed and eyeless forms of A. mexicanus and quantified the thickness of individual retinal layers among 115 F2 hybrid progeny. We used next generation sequencing (RAD-seq) and microsatellite mapping to construct a dense genetic map of the Astyanax genome, scan for quantitative trait loci (QTL) affecting retinal thickness, and identify candidate genes within these QTL regions. The map we constructed for Astyanax includes nearly 700 markers assembled into 25 linkage groups. Based on our scans with this map, we identified four QTL, one each associated with the thickness of the ganglion, inner nuclear, outer plexiform, and outer nuclear layers of the retina. For all but one QTL, cavefish alleles resulted in a clear reduction in the thickness of the affected layer. Comparative mapping of genetic markers within each QTL revealed that each QTL corresponds to an approximately 35 Mb region of the zebrafish genome. Within each region, we identified several candidate genes associated with the function of each affected retinal layer. Our study is the first to examine Astyanax retinal degeneration in the context of QTL mapping. The regions we identify serve as a starting point for future studies on the genetics of retinal degeneration and eye disease using the evolutionary mutant model Astyanax. PMID:23437360

  5. Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus.

    PubMed

    O'Quin, Kelly E; Yoshizawa, Masato; Doshi, Pooja; Jeffery, William R

    2013-01-01

    The retina is the light-sensitive tissue of the eye that facilitates vision. Mutations within genes affecting eye development and retinal function cause a host of degenerative visual diseases, including retinitis pigmentosa and anophthalmia/microphthalmia. The characin fish Astyanax mexicanus includes both eyed (surface fish) and eyeless (cavefish) morphs that initially develop eyes with normal retina; however, early in development, the eyes of cavefish degenerate. Since both surface and cave morphs are members of the same species, they serve as excellent evolutionary mutant models with which to identify genes causing retinal degeneration. In this study, we crossed the eyed and eyeless forms of A. mexicanus and quantified the thickness of individual retinal layers among 115 F(2) hybrid progeny. We used next generation sequencing (RAD-seq) and microsatellite mapping to construct a dense genetic map of the Astyanax genome, scan for quantitative trait loci (QTL) affecting retinal thickness, and identify candidate genes within these QTL regions. The map we constructed for Astyanax includes nearly 700 markers assembled into 25 linkage groups. Based on our scans with this map, we identified four QTL, one each associated with the thickness of the ganglion, inner nuclear, outer plexiform, and outer nuclear layers of the retina. For all but one QTL, cavefish alleles resulted in a clear reduction in the thickness of the affected layer. Comparative mapping of genetic markers within each QTL revealed that each QTL corresponds to an approximately 35 Mb region of the zebrafish genome. Within each region, we identified several candidate genes associated with the function of each affected retinal layer. Our study is the first to examine Astyanax retinal degeneration in the context of QTL mapping. The regions we identify serve as a starting point for future studies on the genetics of retinal degeneration and eye disease using the evolutionary mutant model Astyanax. PMID:23437360

  6. Characterization of a transformed rat retinal ganglion cell line.

    PubMed

    Krishnamoorthy, R R; Agarwal, P; Prasanna, G; Vopat, K; Lambert, W; Sheedlo, H J; Pang, I H; Shade, D; Wordinger, R J; Yorio, T; Clark, A F; Agarwal, N

    2001-01-31

    The purpose of the present study was to establish a rat retinal ganglion cell line by transformation of rat retinal cells. For this investigation, retinal cells were isolated from postnatal day 1 (PN1) rats and transformed with the psi2 E1A virus. In order to isolate retinal ganglion cells (RGC), single cell clones were chosen at random from the transformed cells. Expression of Thy-1 (a marker for RGC), glial fibrillary acidic protein (GFAP, a positive marker for Muller cells), HPC-1/syntaxin (a marker for amacrine cells), 8A1 (a marker for horizontal and ganglion cells) and neurotrophins was studied using reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunocytochemistry. One of the retinal cell clones, designated RGC-5, was positive for Thy-1, Brn-3C, Neuritin, NMDA receptor, GABA-B receptor, and synaptophysin expression and negative for GFAP, HPC-1, and 8A1, suggesting that it represented a putative RGC clone. The results of RT-PCR analysis were confirmed by immunocytochemistry for Thy-1 and GFAP. Upon further characterization by immunoblotting, the RGC-5 clone was positive for Thy-1, negative for GFAP, 8A1 and syntaxin. RGC 5 cells were also positive for the expression of neurotrophins and their cognate receptors. To establish the physiological relevance of RGC-5, the effects of serum/trophic factor deprivation and glutamate toxicity were analyzed to determine if these cells would undergo apoptosis. The protective effects of neurotrophins on RGC-5 after serum deprivation was also investigated. Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated fluoresceinated dUTP nick end labeling (TUNEL). Serum deprivation resulted in apoptosis and supplementation with both BDNF and NT-4 in the growth media, protected the RGC-5 cells from undergoing apoptosis. On differentiation with succinyl concanavalin A (sConA), RGC-5 cells became sensitive to glutamate toxicity, which could be reversed by inclusion of ciplizone (MK801

  7. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

    PubMed

    Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

    2016-05-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  8. Multiple Independent Oscillatory Networks in the Degenerating Retina.

    PubMed

    Euler, Thomas; Schubert, Timm

    2015-01-01

    During neuronal degenerative diseases, microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. This can be particularly well observed in the retina, where photoreceptor degeneration triggers rewiring of connections in the retina's first synaptic layer (e.g., Strettoi et al., 2003; Haq et al., 2014), while the synaptic organization of inner retinal circuits appears to be little affected (O'Brien et al., 2014; Figures 1A,B). Remodeling of (outer) retinal circuits and diminishing light-driven activity due to the loss of functional photoreceptors lead to spontaneous activity that can be observed at different retinal levels (Figure 1C), including the retinal ganglion cells, which display rhythmic spiking activity in the degenerative retina (Margolis et al., 2008; Stasheff, 2008; Menzler and Zeck, 2011; Stasheff et al., 2011). Two networks have been suggested to drive the oscillatory activity in the degenerating retina: a network of remnant cone photoreceptors, rod bipolar cells (RBCs) and horizontal cells in the outer retina (Haq et al., 2014), and the AII amacrine cell-cone bipolar cell network in the inner retina (Borowska et al., 2011). Notably, spontaneous rhythmic activity in the inner retinal network can be triggered in the absence of synaptic remodeling in the outer retina, for example, in the healthy retina after photo-bleaching (Menzler et al., 2014). In addition, the two networks show remarkable differences in their dominant oscillation frequency range as well as in the types and numbers of involved cells (Menzler and Zeck, 2011; Haq et al., 2014). Taken together this suggests that the two networks are self-sustained and can be active independently from each other. However, it is not known if and how they modulate each other. In this mini review, we will discuss: (i) commonalities and differences between these two oscillatory networks as well as possible interaction pathways; (ii) how multiple self

  9. The morphology, topography and cytoarchitectonics of the ciliary ganglion in the domestic turkey (Meleagris gallopavo domesticus).

    PubMed

    Radzimirska, Małgorzata

    2003-11-01

    The ciliary ganglion of the domestic turkey (Meleagris gallopavo domesticus) is located between the posterior wall of the eyeball and the optic nerve. It is closely connected with the oculomotor nerve; in particular with its inferior branch. The ganglion has a cask-like shape and is adjacent to the inferior branch of the oculomotor nerve. From this ganglion postganglionic fibres emerge which are arranged in two fasciculi. These are termed the long ciliary nerves and the short ciliary nerves. A cross-section of the ciliary ganglion revealed two populations of cells: small ones - choroid cells and large ones - ciliary cells.

  10. An intrinsic neural oscillator in the degenerating mouse retina.

    PubMed

    Borowska, Joanna; Trenholm, Stuart; Awatramani, Gautam B

    2011-03-30

    The loss of photoreceptors during retinal degeneration (RD) is known to lead to an increase in basal activity in remnant neural networks. To identify the source of activity, we combined two-photon imaging with patch-clamp techniques to examine the physiological properties of morphologically identified retinal neurons in a mouse model of RD (rd1). Analysis of activity in rd1 ganglion cells revealed sustained oscillatory (∼10 Hz) synaptic activity in ∼30% of all classes of cells. Oscillatory activity persisted after putative inputs from residual photoreceptor, rod bipolar cell, and inhibitory amacrine cell synapses were pharmacologically blocked, suggesting that presynaptic cone bipolar cells were intrinsically active. Examination of presynaptic rd1 ON and OFF bipolar cells indicated that they rested at relatively negative potentials (less than -50 mV). However, in approximately half the cone bipolar cells, low-amplitude membrane oscillation (∼5 mV, ∼10 Hz) were apparent. Such oscillations were also observed in AII amacrine cells. Oscillations in ON cone bipolar and AII amacrine cells exhibited a weak apparent voltage dependence and were resistant to blockade of synaptic receptors, suggesting that, as in wild-type retina, they form an electrically coupled network. In addition, oscillations were insensitive to blockers of voltage-gated Ca(2+) channels (0.5 mm Cd(2+) and 0.5 mm Ni(2+)), ruling out known mechanisms that underlie oscillatory behavior in bipolar cells. Together, these results indicate that an electrically coupled network of ON cone bipolar/AII amacrine cells constitutes an intrinsic oscillator in the rd1 retina that is likely to drive synaptic activity in downstream circuits.

  11. Neurotrophin-3 transduction attenuates cisplatin spiral ganglion neuron ototoxicity in the cochlea.

    PubMed

    Bowers, William J; Chen, Xiaowei; Guo, Huang; Frisina, D Robert; Federoff, Howard J; Frisina, Robert D

    2002-07-01

    Ototoxicity is a major dose-limiting side effect of cisplatin chemotherapy for cancer patients. We previously demonstrated in vitro that herpes simplex type 1 (HSV-1) amplicon-mediated delivery of a neurotrophin-3 (NT-3)/myc chimera protects spiral ganglion neurons (SGNs) in murine cochlear cultures from cisplatin-induced ototoxicity. To extend these findings, a newly constructed amplicon vector (HSVnt-3myc/SV40lac) that expresses the NT-3myc chimera and the Escherichia coli beta-galactosidase (lacZ) reporter gene under separate transcriptional control was initially tested in vitro and then was delivered to the cochlea of aged mice that were subsequently treated with cisplatin. Successful transduction with the new amplicon was observed in vitro as determined by its capacity to infect SGNs and to express NT-3myc mRNA and protein. To determine whether amplicon-directed NT-3myc overexpression could abrogate the ototoxicity in vivo, two groups of aged mice (CBA) were inoculated with HSVnt-3myc/SV40lac or control vector, HSVSV40lac, preceding administration of cisplatin. Cochleas inoculated with HSVnt-3myc/SV40lac harbored significantly greater numbers of surviving SGNs and showed lower incidence of cisplatin-induced apoptosis or necrosis than those injected with the control virus. These data demonstrate that HSV amplicon-mediated NT-3 delivery can attenuate the ototoxic actions of cisplatin in the peripheral auditory system of the aged mouse. The potency of NT-3 in SGN neuroprotection suggests that in vivo neurotrophin-based gene therapy is a promising preventative treatment for chemical-induced hearing disorders, and potentially for hearing degeneration due to normal aging.

  12. Degeneration of biogenic superparamagnetic magnetite.

    PubMed

    Li, Y-L; Pfiffner, S M; Dyar, M D; Vali, H; Konhauser, K; Cole, D R; Rondinone, A J; Phelps, T J

    2009-01-01

    Magnetite crystals precipitated as a consequence of Fe(III) reduction by Shewanella algae BrY after 265 h incubation and 5-year anaerobic storage were investigated with transmission electron microscopy, Mössbauer spectroscopy and X-ray diffraction. The magnetite crystals were typically superparamagnetic with an approximate size of 13 nm. The lattice constants of the 265 h and 5-year crystals are 8.4164A and 8.3774A, respectively. The Mössbauer spectra indicated that the 265 h magnetite had excess Fe(II) in its crystal-chemistry (Fe(3+) (1.990)Fe(2+) (1.015)O(4)) but the 5-year magnetite was Fe(II)-deficient in stoichiometry (Fe(3+) (2.388)Fe(2+) (0.419)O(4)). Such crystal-chemical changes may be indicative of the degeneration of superparamagnetic magnetite through the aqueous oxidization of Fe(II) anaerobically, and the concomitant oxidation of the organic phases (fatty acid methyl esters) that were present during the initial formation of the magnetite. The observation of a corona structure on the aged magnetite corroborates the anaerobic oxidation of Fe(II) on the outer layers of magnetite crystals. These results suggest that there may be a possible link between the enzymatic activity of the bacteria and the stability of Fe(II)-excess magnetite, which may help explain why stable nano-magnetite grains are seldom preserved in natural environments.

  13. Modified gravitational instability of degenerate and non-degenerate dusty plasma

    NASA Astrophysics Data System (ADS)

    Jain, Shweta; Sharma, Prerana

    2016-09-01

    The gravitational instability of strongly coupled dusty plasma (SCDP) is studied considering degenerate and non-degenerate dusty plasma situations. The SCDP system is assumed to be composed of the electrons, ions, neutrals, and strongly coupled dust grains. First, in the high density regime, due to small interparticle distance, the electrons are considered degenerate, whereas the neutrals, dust grains, and ions are treated non-degenerate. In this case, the dynamics of inertialess electrons are managed by Fermi pressure and Bohm potential, while the inertialess ions are by only thermal pressure. Second, in the non-degenerate regime, both the electrons and ions are governed by the thermal pressure. The generalized hydrodynamic model and the normal mode analysis technique are employed to examine the low frequency waves and gravitational instability in both degenerate and non-degenerate cases. The general dispersion relation is discussed for a characteristic timescale which provides two regimes of frequency, i.e., hydrodynamic regime and kinetic regime. Analytical solutions reveal that the collisions reduce the growth rate and have a strong impact on structure formation in both degenerate and non-degenerate circumstances. Numerical estimation on the basis of observed parameters for the degenerate and non-degenerate cases is presented to show the effects of dust-neutral collisions and dust effective velocity in the presence of polarization force. The values of Jeans length and Jeans mass have been estimated for degenerate white dwarfs as Jeans length L J = 1.3 × 10 5 cm and Jeans mass M J = 0.75 × 10 - 3 M⊙ and for non-degenerate laboratory plasma Jeans length L J = 6.86 × 10 16 cm and Jeans mass M J = 0.68 × 10 10 M⊙. The stability of the SCDP system is discussed using the Routh-Hurwitz criterion.

  14. Total absorption by degenerate critical coupling

    SciTech Connect

    Piper, Jessica R. Liu, Victor; Fan, Shanhui

    2014-06-23

    We consider a mirror-symmetric resonator with two ports. We show that, when excited from a single port, complete absorption can be achieved through critical coupling to degenerate resonances with opposite symmetry. Moreover, any time two resonances with opposite symmetry are degenerate in frequency and absorption is always significantly enhanced. In contrast, when two resonances with the same symmetry are nearly degenerate, there is no absorption enhancement. We numerically demonstrate these effects using a graphene monolayer on top of a photonic crystal slab, illuminated from a single side in the near-infrared.

  15. Horizon supertranslation and degenerate black hole solutions

    NASA Astrophysics Data System (ADS)

    Cai, Rong-Gen; Ruan, Shan-Ming; Zhang, Yun-Long

    2016-09-01

    In this note we first review the degenerate vacua arising from the BMS symmetries. According to the discussion in [1] one can define BMS-analogous supertranslation and superrotation for spacetime with black hole in Gaussian null coordinates. In the leading and subleading orders of near horizon approximation, the infinitely degenerate black hole solutions are derived by considering Einstein equations with or without cosmological constant, and they are related to each other by the diffeomorphism generated by horizon supertranslation. Higher order results and degenerate Rindler horizon solutions also are given in appendices.

  16. Advances in the management of macular degeneration

    PubMed Central

    2014-01-01

    Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition. PMID:24860651

  17. The Sphenopalatine Ganglion: Anatomy, Pathophysiology, and Therapeutic Targeting in Headache.

    PubMed

    Robbins, Matthew S; Robertson, Carrie E; Kaplan, Eugene; Ailani, Jessica; Charleston, Larry; Kuruvilla, Deena; Blumenfeld, Andrew; Berliner, Randall; Rosen, Noah L; Duarte, Robert; Vidwan, Jaskiran; Halker, Rashmi B; Gill, Nicole; Ashkenazi, Avi

    2016-02-01

    The sphenopalatine ganglion (SPG) has attracted the interest of practitioners treating head and face pain for over a century because of its anatomical connections and role in the trigemino-autonomic reflex. In this review, we discuss the anatomy of the SPG, as well as what is known about its role in the pathophysiology of headache disorders, including cluster headache and migraine. We then address various therapies that target the SPG, including intranasal medication delivery, new SPG blocking catheter devices, neurostimulation, chemical neurolysis, and ablation procedures.

  18. Frontotemporal lobar degeneration: current perspectives

    PubMed Central

    Riedl, Lina; Mackenzie, Ian R; Förstl, Hans; Kurz, Alexander; Diehl-Schmid, Janine

    2014-01-01

    The term frontotemporal lobar degeneration (FTLD) refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer’s disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN), and in the chromosome 9 open reading frame 72 (C9orf72) accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management. PMID:24600223

  19. [Cystic degeneration of autonomous adenomas (author's transl)].

    PubMed

    Galvan, G; Pohl, G B

    1976-01-01

    Follow-up examinations in four patients with autonomous adenomas showed cystic degeneration in the autonomous adenomas 20 to 45 months after the first examination, confirmed by fine needle biopsy. Clinical improvement occurred three times with scintigraphic compensation, decompensation occurred once without clinical deterioration. In particular cases a therapeutic policy of wait and see is justified in patients with autonomous adenomas because they may remain clinically inconspicuous for a long time; on the other hand there is a possibility of a cystic degeneration.

  20. Ganglionic adrenergic action modulates ovarian steroids and nitric oxide in prepubertal rat.

    PubMed

    Delgado, Silvia Marcela; Casais, Marilina; Sosa, Zulema; Rastrilla, Ana María

    2006-08-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. The purpose of this work was to analyse the ganglionic adrenergic influence on the ovarian release of steroids and NO and the possible steroids/NO relationship. The experiments were carried out in the ex vivo coeliac ganglion-superior ovarian nerve (SON)-ovary system of prepubertal rats. The coeliac ganglion-SON-ovary system was incubated in Krebs Ringer-bicarbonate buffer in presence of adrenergic agents in the ganglionic compartment. The accumulation of progesterone, androstenedione, oestradiol and NO in the ovarian incubation liquid was measured. Norepinephrine in coeliac ganglion inhibited the liberation of progesterone and increased androstenedione, oestradiol and NO in ovary. The addition of alpha and beta adrenergic antagonists also showed different responses in the liberation of the substances mentioned before, which, from a physiological point of view, reveals the presence of adrenergic receptors in coeliac ganglion. In relation to propranolol, it does not revert the effect of noradrenaline on the liberation of progesterone, which leads us to think that it might also have a "per se" effect on the ganglion, responsible for the ovarian response observed for progesterone. Finally, we can conclude that the ganglionic adrenergic action via SON participates on the regulation of the prepubertal ovary in one of two ways: either increasing the NO, a gaseous neurotransmitter with cytostatic characteristics, to favour the immature follicles to remain dormant or increasing the liberation of androstenedione and oestradiol, the steroids necessary for the beginning of the near first estral cycle.

  1. Phenol cauterization for ganglions of the hand, wrist, and foot: a preliminary report.

    PubMed

    Park, S; Iida, T; Yoshimura, K; Kawasaki, Y

    2002-06-01

    Many methods have been reported for the treatment of ganglions. The authors present their modified technique for ganglion sclerotherapy. Their modification enables them to perform sclerotherapy safely and consistently, and they have treated 10 patients in this manner. The method is described and the cases are illustrated.

  2. Macro and microstructural organization of the dog's caudal mesenteric ganglion complex (Canis familiaris-Linnaeus, 1758).

    PubMed

    Gagliardo, K M; Guidi, W L; Da Silva, R A; Ribeiro, A A C M

    2003-08-01

    The caudal mesenteric ganglion (CMG) is located ventral to the abdominal aorta involving the initial portion of the caudal mesenteric artery. Its macro and microstructural organization was studied in 40 domestic dogs. From the CMG, there were three nerves: the main hypogastric, the left hypogastric and the right hypogastric. The main hypogastric nerve emits two branches: the left colonic nerve and the cranial rectal nerve. Afterwards they give rise to branches to the descending colon (colonic nerves) and rectum (rectal nerves). The cranial rectal nerve, and left and right hypogastric nerves were directed to the pelvic ganglia. The microscopic study permitted the observation of the histological organization of the CMG, which is a ganglionic complex composed of an agglomeration of ganglionic units. Each ganglionic unit is composed of three major cell types: principal ganglion neurones (PGNs), glial cells and small intensely fluorescent (SIF) cells, and they were separated by nerve fibres, septa of connective tissue (types 1 and 3 collagen fibres), fibroblasts and intraganglionic capillaries. Hence, the ganglionic unit is the morphological support for the microstructural organization of the CMG complex. Further, each ganglionic unit is constituted by a cellular triad (SIF cells, PGN and glial cells), which is the cytological basis for each ganglionic unit.

  3. Sympathetic and sensory innervation of small intensely fluorescent (SIF) cells in rat superior cervical ganglion.

    PubMed

    Takaki, Fumiya; Nakamuta, Nobuaki; Kusakabe, Tatsumi; Yamamoto, Yoshio

    2015-02-01

    The sympathetic ganglion contains small intensely fluorescent (SIF) cells derived from the neural crest. We morphologically characterize SIF cells and focus on their relationship with ganglionic cells, preganglionic nerve fibers and sensory nerve endings. SIF cells stained intensely for tyrosine hydroxylase (TH), with a few cells also being immunoreactive for dopamine β-hydroxylase (DBH). Vesicular acetylcholine transporter (VAChT)-immunoreactive puncta were distributed around some clusters of SIF cells, whereas some SIF cells closely abutted DBH-immunoreactive ganglionic cells. SIF cells contained bassoon-immunoreactive products beneath the cell membrane at the attachments and on opposite sites to the ganglionic cells. Ganglion neurons and SIF cells were immunoreactive to dopamine D2 receptors. Immunohistochemistry for P2X3 revealed ramified nerve endings with P2X3 immunoreactivity around SIF cells. Triple-labeling for P2X3, TH and VAChT allowed the classification of SIF cells into three types based on their innervation: (1) with only VAChT-immunoreactive puncta, (2) with only P2X3-immunoreactive nerve endings, (3) with both P2X3-immunoreactive nerve endings and VAChT-immunoreactive puncta. The results of retrograde tracing with fast blue dye indicated that most of these nerve endings originated from the petrosal ganglion. Thus, SIF cells in the superior cervical ganglion are innervated by preganglionic fibers and glossopharyngeal sensory nerve endings and can be classified into three types. SIF cells might modulate sympathetic activity in the superior cervical ganglion. PMID:25416508

  4. Virus-like particles associated with intracardiac ganglionitis in 2 cases of sudden unexpected death.

    PubMed

    James, T N; Imamura, K

    1981-05-01

    Two previously healthy young individuals died suddenly and unexpectedly, and in both of them there was ganglionitis in the heart, especially near the sinus node. Electron microscopic examination demonstrated virus-like particles in the vicinity of the ganglionitis of both hearts. Viral cardioneuropathy may play a role in the pathogenesis of sudden unexpected deaths and deserves further investigation.

  5. Ganglion and Synovial Cyst of the Temporomandibular Joint: A Case Report and Literature Review.

    PubMed

    Steen, M Willemijn; Hofstede, Diederik J

    2015-09-01

    Ganglion and synovial cysts of the temporomandibular joint (TMJ) are rare. Although histopathological findings differ, clinical presentation is comparable. This study adds a case report of a ganglion of the TMJ to existing literature and a review of all available case reports on ganglion and synovial cysts of the TMJ. Including our own case report, we reviewed 49 cases of ganglion and synovial cysts of the TMJ. They occurred in a female:male ratio of 3:1, at an median age of 46 years (range, 11-64 years). Patients mainly presented with preauricular swelling and pain. After imaging, the ganglion or synovial cyst was most commonly excised under general anesthesia. No recurrences were described. PMID:26495237

  6. Ganglion and Synovial Cyst of the Temporomandibular Joint: A Case Report and Literature Review

    PubMed Central

    Hofstede, Diederik J.

    2015-01-01

    Summary: Ganglion and synovial cysts of the temporomandibular joint (TMJ) are rare. Although histopathological findings differ, clinical presentation is comparable. This study adds a case report of a ganglion of the TMJ to existing literature and a review of all available case reports on ganglion and synovial cysts of the TMJ. Including our own case report, we reviewed 49 cases of ganglion and synovial cysts of the TMJ. They occurred in a female:male ratio of 3:1, at an median age of 46 years (range, 11–64 years). Patients mainly presented with preauricular swelling and pain. After imaging, the ganglion or synovial cyst was most commonly excised under general anesthesia. No recurrences were described. PMID:26495237

  7. The spiral ganglion and Rosenthal's canal in beluga whales.

    PubMed

    Sensor, Jennifer D; Suydam, Robert; George, John C; Liberman, M C; Lovano, Denise; Rhaganti, Mary Ann; Usip, Sharon; Vinyard, Christopher J; Thewissen, J G M

    2015-12-01

    With the increase of human activity and corresponding increase in anthropogenic sounds in marine waters of the Arctic, it is necessary to understand its effect on the hearing of marine wildlife. We have conducted a baseline study on the spiral ganglion and Rosenthal's canal of the cochlea in beluga whales (Delphinapterus leucas) as an initial assessment of auditory anatomy and health. We present morphometric data on the length of the cochlea, number of whorls, neuron densities along its length, Rosenthal's canal length, and cross-sectional area, and show some histological results. In belugas, Rosenthal's canal is not a cylinder of equal cross-sectional area, but its cross-section is greatest near the apex of the basal whorl. We found systematic variation in the numbers of neurons along the length of the spiral ganglion, indicating that neurons are not dispersed evenly in Rosenthal's canal. These results provide data on functionally important structural parameters of the beluga ear. We observed no signs of acoustic trauma in our sample of beluga whales.

  8. Petrosal ganglion: a more complex role than originally imagined.

    PubMed

    Retamal, Mauricio A; Reyes, Edison P; Alcayaga, Julio

    2014-01-01

    The petrosal ganglion (PG) is a peripheral sensory ganglion, composed of pseudomonopolar sensory neurons that innervate the posterior third of the tongue and the carotid sinus and body. According to their electrical properties PG neurons can be ascribed to one of two categories: (i) neurons with action potentials presenting an inflection (hump) on its repolarizing phase and (ii) neurons with fast and brisk action potentials. Although there is some correlation between the electrophysiological properties and the sensory modality of the neurons in some species, no general pattern can be easily recognized. On the other hand, petrosal neurons projecting to the carotid body are activated by several transmitters, with acetylcholine and ATP being the most conspicuous in most species. Petrosal neurons are completely surrounded by a multi-cellular sheet of glial (satellite) cells that prevents the formation of chemical or electrical synapses between neurons. Thus, PG neurons are regarded as mere wires that communicate the periphery (i.e., carotid body) and the central nervous system. However, it has been shown that in other sensory ganglia satellite glial cells and their neighboring neurons can interact, partly by the release of chemical neuro-glio transmitters. This intercellular communication can potentially modulate the excitatory status of sensory neurons and thus the afferent discharge. In this mini review, we will briefly summarize the general properties of PG neurons and the current knowledge about the glial-neuron communication in sensory neurons and how this phenomenon could be important in the chemical sensory processing generated in the carotid body.

  9. The spiral ganglion and Rosenthal's canal in beluga whales.

    PubMed

    Sensor, Jennifer D; Suydam, Robert; George, John C; Liberman, M C; Lovano, Denise; Rhaganti, Mary Ann; Usip, Sharon; Vinyard, Christopher J; Thewissen, J G M

    2015-12-01

    With the increase of human activity and corresponding increase in anthropogenic sounds in marine waters of the Arctic, it is necessary to understand its effect on the hearing of marine wildlife. We have conducted a baseline study on the spiral ganglion and Rosenthal's canal of the cochlea in beluga whales (Delphinapterus leucas) as an initial assessment of auditory anatomy and health. We present morphometric data on the length of the cochlea, number of whorls, neuron densities along its length, Rosenthal's canal length, and cross-sectional area, and show some histological results. In belugas, Rosenthal's canal is not a cylinder of equal cross-sectional area, but its cross-section is greatest near the apex of the basal whorl. We found systematic variation in the numbers of neurons along the length of the spiral ganglion, indicating that neurons are not dispersed evenly in Rosenthal's canal. These results provide data on functionally important structural parameters of the beluga ear. We observed no signs of acoustic trauma in our sample of beluga whales. PMID:26769322

  10. Neuroanatomy and neurophysiology of the locust hypocerebral ganglion.

    PubMed

    Rand, David; Ayali, Amir

    2010-08-01

    The insect stomatogastric ganglia control foregut movements. Most previous work on the system has concentrated on the frontal ganglion (FG), including research into the role of the FG in feeding as well as molting-related behavior, mostly in locusts, but also in other insect species. The stomatogastric system exerts its physiological actions by way of careful interaction and coordination between its different neural centers and pattern-generating circuits. One such hitherto unstudied neural center is the hypocerebral ganglion (HG), which is connected to the FG via the recurrent nerve. It sends two pairs of nerves along the esophagus and to the posterior region of the crop, terminating in the paired ingluvial ganglia. Very little is known about the neuroanatomy and neurophysiology of the insect HG. Here we investigate, for the first time, the neuronal composition of the locust HG, as well as its motor output. We identify rhythmic patterns endogenous to the isolated HG, demonstrating the presence of a central pattern-generating network. Our findings suggest interactions between the HG and FG rhythm-generating circuits leading to complex physiological actions of both ganglia. This work will serve as a basis for future investigation into the physiology of the HG and its role in insect behavior.

  11. Omitting histopathology in wrist ganglions. A risky proposition

    PubMed Central

    Zubairi, Akbar J.; Kumar, Santosh; Mohib, Yasir; Rashid, Rizwan H.; Noordin, Shahryar

    2016-01-01

    Objectives: To identify incidence and utility of histopathology in wrist ganglions. Methods: A retrospective study of 112 patients operated for wrist swellings between January 2009 and March 2014 at Aga Khan University Hospital, Karachi, Pakistan, was conducted. Medical records were reviewed for demographics, history, location and associated symptoms, provisional diagnosis and operative details. Histopathology reports were reviewed to confirm the final diagnosis. Results: One hundred and twelve patients were included in the study (34 males and 78 females) with a mean age of 28 ± 12 years. Ninety-five percent of ganglia were dorsally located and 85% were solitary in nature. Histopathology reports confirmed 107 as ganglion cysts, whereas 3 had giant cell tumor of tendon sheath and 2 were reported to be tuberculous tenosynovitis. Conclusion: Although most of the time, the clinical diagnosis conforms to the final diagnosis, the possibility of an alternate diagnosis cannot be ignored (4% in this study). We suggest routine histopathological analysis so that such diagnoses are not missed. PMID:27464871

  12. The functional diversity of retinal ganglion cells in the mouse

    PubMed Central

    Baden, Tom; Berens, Philipp; Franke, Katrin; Rosón, Miroslav Román; Bethge, Matthias; Euler, Thomas

    2015-01-01

    SUMMARY In the vertebrate visual system, all output of the retina is carried by retinal ganglion cells. Each type encodes distinct visual features in parallel for transmission to the brain. How many such “output channels” exist and what each encodes is an area of intense debate. In mouse, anatomical estimates range between 15–20 channels, and only a handful are functionally understood. Combining two-photon calcium imaging to obtain dense retinal recordings and unsupervised clustering of the resulting sample of >11,000 cells, we here show that the mouse retina harbours substantially more than 30 functional output channels. These include all known and several new ganglion cell types, as verified by genetic and anatomical criteria. Therefore, information channels from the mouse’s eye to the mouse’s brain are considerably more diverse than shown thus far by anatomical studies, suggesting an encoding strategy resembling that used in state-of-the-art artificial vision systems. PMID:26735013

  13. Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration.

    PubMed

    Greferath, Ursula; Anderson, Emily E; Jobling, Andrew I; Vessey, Kirstan A; Martinez, Gemma; de Iongh, Robb U; Kalloniatis, Michael; Fletcher, Erica L

    2015-01-01

    While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL) mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a mutation in the phosphodiesterase gene, Pde6b, and an axonally targeted transgenic beta galactosidase reporter system under the control of the c-fos promoter. Retinae of transgenic rd1-FTL mice and control FTL animals aged 2-12 months were processed for indirect fluorescence immunocytochemistry. At 2 months of age, a time when the majority of photoreceptor nuclei are lost, there was negligible c-fos reporter (FTL) expression, however, from 4 months, reporter expression was observed to increase within subpopulations of amacrine and ganglion cells within the central retina. These areas of inner retinal FTL expression coincided with regions that contained aberrant Müller cells. Specifically, these cells exhibited reduced glutamine synthetase and Kir4.1 immunolabelling, whilst showing evidence of proliferative gliosis (increased cyclinD1 and glial fibrillary acidic protein expression). These changes were limited to distinct regions where cone photoreceptor terminals were absent. Overall, these results highlight that distinct areas of the rd1-FTL central retina undergo significant glial alterations after cone photoreceptor loss. These areas coincide with up-regulation of the c-fos reporter in the inner retina, which may represent a change in neuronal function/plasticity. The rd1-FTL mouse is a useful model system to probe changes that occur in the inner retina at later stages of retinal degeneration. PMID:26283925

  14. Three Ca2+ channel inhibitors in combination limit chronic secondary degeneration following neurotrauma.

    PubMed

    Savigni, Donna L; O'Hare Doig, Ryan L; Szymanski, Charis R; Bartlett, Carole A; Lozić, Ivan; Smith, Nicole M; Fitzgerald, Melinda

    2013-12-01

    Following neurotrauma, cells beyond the initial trauma site undergo secondary degeneration, with excess Ca2+ a likely trigger for loss of neurons, compact myelin and function. Treatment using inhibitors of specific Ca2+ channels has shown promise in preclinical studies, but clinical trials have been disappointing and combinatorial approaches are needed. We assessed efficacy of multiple combinations of three Ca2+ channel inhibitors at reducing secondary degeneration following partial optic nerve transection in rat. We used lomerizine to inhibit voltage gated Ca2+ channels; oxidised adenosine-triphosphate (oxATP) to inhibit purinergic P2X7 receptors and/or 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-1,2,3,4-tetrahydro quinoxalin-1-yl]acetic acid (INQ) to inhibit Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Only the three Ca2+ channel inhibitors delivered in combination significantly preserved visual function, as assessed using the optokinetic nystagmus visual reflex, at 3 months after injury. Preservation of retinal ganglion cells was partial and is unlikely to have accounted for differential effects on function. A range of the Ca2+ channel inhibitor combinations prevented swelling of optic nerve vulnerable to secondary degeneration. Each of the treatments involving lomerizine significantly increased the proportion of axons with normal compact myelin. Nevertheless, limiting decompaction of myelin was not sufficient for preservation of function in our model. Multiple combinations of Ca2+ channel inhibitors reduced formation of atypical node/paranode complexes; outcomes were not associated with preservation of visual function. However, prevention of lengthening of the paranodal gap that was only achieved by treatment with the three Ca2+ channel inhibitors in combination was an important additional effect that likely contributed to the associated preservation of the optokinetic reflex using this combinatorial treatment strategy

  15. Inhibiting Matrix Metalloproteinase 3 Ameliorates Neuronal Loss in the Ganglion Cell Layer of Rats in Retinal Ischemia/Reperfusion.

    PubMed

    Hu, Tu; You, Qiuting; Chen, Dan; Tong, Jianbin; Shang, Lei; Luo, Jia; Qiu, Yi; Yu, Huimin; Zeng, Leping; Huang, Jufang

    2016-05-01

    It has been demonstrated that matrix metalloproteinase 3 (MMP3) is integrally involved in the neuronal degeneration of the central nervous system by promoting glial activation, neuronal apoptosis and damage to the brain-blood barrier. However, whether MMP3 also contributes to the neuronal degeneration induced by retinal ischemia/reperfusion is still uncertain. In the present study, we detected the cellular localization of MMP3 in adult rat retinae and explored the relationship of its expression with neuronal loss in the ganglion cell layer (GCL) in retinal ischemia/reperfusion. We found that MMP3 was widely expressed in many cells throughout the layers of the rat retinae, including Vertebrate neuron-specific nuclear protein (NeuN)-, parvalbumin-, calbindin-, protein kinase C-α-, glial fibrillary acidic protein-, glutamine synthetase- and CD11b-positive cells. Furthermore, all rats were treated with high intraocular pressure (HIOP) for 1 h (h) and sacrificed at 6 h, 1 day (d), 3 d, and 7 d after HIOP. Compared to the normal control, the expression of both proenzyme MMP3 and active MMP3 were significantly up-regulated after HIOP treatment without alteration of the laminar distribution pattern. Moreover, inhibiting MMP3 ameliorated the loss of NeuN-positive cells in the GCL following HIOP. In summary, our data demonstrates that MMP3 is expressed in multiple types of neurons and glial cells in normal rat retinae. Simultaneously, the up-regulation of its expression and activity are closely involved in neuronal loss in the GCL in retinal ischemia/reperfusion. PMID:26830289

  16. Proteomic Identification of Proteins Suggestive of Immune-Mediated Response or Neuronal Degeneration in Serum of Achalasia Patients

    PubMed Central

    Im, Seon Kyo; Yeo, Mari

    2013-01-01

    Background/Aims The primary pathophysiologic abnormality in achalasia is known to be a loss of inhibitory myenteric ganglion cells, which may result from an immune-mediated response or neuronal degeneration. The aim of this study was to identify proteins suggestive of an immune-mediated response or neuronal degeneration in the serum of achalasia patients using a proteomic analysis. Methods Blood samples were collected from five symptomatic achalasia patients and five sex- and age-matched healthy controls. Serum proteomic analysis was conducted, and the protein spots were identified using matrix-assisted laser desorption ionization/time-of-flight and a proteomics analyzer. The serum level of C3 was measured by enzyme-linked immunosorbent assay in nine patients with achalasia and 18 sex- and age-matched healthy controls. Results Of the 658 matched protein spots, 28 spots were up-regulated over 2-fold in the serum from achalasia patients compared with that from controls. The up-regulated proteins included complement C4B5, complement C3, cyclin-dependent kinase 5, transthyretin, and alpha 2 macroglobulin. The serum levels of C3 in achalasia patients were significantly higher than those of controls. Conclusions The serum proteomic analysis of achalasia patients suggests an immune-mediated response or neuronal degeneration. Further validation studies in larger samples and the esophageal tissue of achalasia patients are required. PMID:23898380

  17. The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans.

    PubMed

    Jindahra, Panitha; Petrie, Aviva; Plant, Gordon T

    2012-02-01

    Following damage to the human post-geniculate visual pathway retrograde trans-synaptic degeneration of the optic nerve fibres occurs. It has been known for some time from investigations carried out in primates that a decline in the number of retinal ganglion cells follows occipital lobectomy. However, this is not detectable in all species studied and whether this occurs in humans was controversial until recent studies that have shown that following lesions of the occipital lobe, the retinal nerve fibre layer thickness measured by optical coherence tomography is reduced and corresponding shrinkage of the optic tract can be demonstrated by magnetic resonance imaging. The time course of the degeneration in humans is, however, unknown. In the present study, we have used optical coherence tomography to demonstrate for the first time progressive thinning of the retinal nerve fibre layer following occipital lobe/optic radiation damage due to stroke. First, in a group of 38 patients the measurement was taken on a single occasion at a known time interval since the stroke, ranging from 6 days to 67 years. Here, a negative straight line relationship (linear regression r = 0.54, P < 0.001) was found between nerve fibre layer thickness and elapsed time since injury in log years, giving a rate of decline of 9.08 µm per log year after adjusting for age. This indicates a decelerating rate of loss that differs from the rate of decline found with chronological age in this same group, which shows a steady rate of thinning by 0.4 µm per year (P = 0.006) after adjusting for duration of the disease. In a second study serial measurements were taken following the acute event in a group of seven patients with homonymous hemianopia; here a negative straight line relationship was found between time and nerve fibre layer thickness in micrometres over a period of data collection beginning at a mean of 36.9 days post-stroke (range 5-112) and ending at a mean of 426.6 days post

  18. Prospectives for Gene Therapy of Retinal Degenerations

    PubMed Central

    Thumann, Gabriele

    2012-01-01

    Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell

  19. Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

    PubMed

    Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

    2016-07-01

    Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system.

  20. Isolation and Molecular Profiling of Primary Mouse Retinal Ganglion Cells: Comparison of Phenotypes from Healthy and Glaucomatous Retinas

    PubMed Central

    Chintalapudi, Sumana R.; Djenderedjian, Levon; Stiemke, Andrew B.; Steinle, Jena J.; Jablonski, Monica M.; Morales-Tirado, Vanessa M.

    2016-01-01

    Loss of functional retinal ganglion cells (RGC) is an element of retinal degeneration that is poorly understood. This is in part due to the lack of a reliable and validated protocol for the isolation of primary RGCs. Here we optimize a feasible, reproducible, standardized flow cytometry-based protocol for the isolation and enrichment of homogeneous RGC with the Thy1.2hiCD48negCD15negCD57neg surface phenotype. A three-step validation process was performed by: (1) genomic profiling of 25-genes associated with retinal cells; (2) intracellular labeling of homogeneous sorted cells for the intracellular RGC-markers SNCG, brain-specific homeobox/POU domain protein 3A (BRN3A), TUJ1, and RNA-binding protein with multiple splicing (RBPMS); and (3) by applying the methodology on RGC from a mouse model with elevated intraocular pressure (IOP) and optic nerve damage. Use of primary RGC cultures will allow for future careful assessment of important cell specific pathways in RGC to provide mechanistic insights into the declining of visual acuity in aged populations and those suffering from retinal neurodegenerative diseases. PMID:27242509

  1. A comprehensive negative regulatory program controlled by Brn3b to ensure ganglion cell specification from multipotential retinal precursors.

    PubMed

    Qiu, Feng; Jiang, Haisong; Xiang, Mengqing

    2008-03-26

    The retinal ganglion cells (RGCs) are the sole output neurons in the retina that form the optic nerve and convey light signals detected by photoreceptors to the higher visual system. Their degeneration and damage caused by glaucoma and injury can lead to blindness. During retinogenesis, RGCs are specified from a population of multipotential precursors capable of generating RGC, amacrine, horizontal, and cone cells. How the RGC fate is selected from these multiple neuron fates is unknown at present. Here we show that the previously unsuspected POU domain transcription factor Brn3b (brain-specific homeobox/POU domain protein 3b) plays such a critical role. Loss of Brn3b function in mice leads to misspecification of early RGC precursors as late-born RGC, amacrine, and horizontal cells, whereas misexpressed Brn3b suppresses non-RGC cell fates but promotes the RGC fate. Microarray profiling and other molecular analyses reveal that, in RGC precursors, Brn3b normally represses the expression of a network of retinogenic factor genes involved in fate commitment and differentiation of late-born RGC, amacrine, horizontal, and cone cells. Our data suggest that Brn3b specifies the RGC fate from multipotential precursors not only by promoting RGC differentiation but also by suppressing non-RGC differentiation programs as a safeguard mechanism. PMID:18367606

  2. Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

    PubMed Central

    Madeira, Maria H.; Ortin-Martinez, Arturo; Nadal-Nícolas, Francisco; Ambrósio, António F.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Santiago, Ana Raquel

    2016-01-01

    Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID:27270337

  3. Nuclear Atrophy of Retinal Ganglion Cells Precedes the Bax-Dependent Stage of Apoptosis

    PubMed Central

    Janssen, Katherine T.; Mac Nair, Caitlin E.; Dietz, Joel A.; Schlamp, Cassandra L.; Nickells, Robert W.

    2013-01-01

    Purpose. Retinal ganglion cells atrophy during the execution of the intrinsic apoptotic program. This process, which has been termed the apoptotic volume decrease (AVD) in other cell types, has not been well-characterized in ganglion cells. Methods. Acute optic nerve crush was used to examine neuronal atrophy in the ganglion cell layer in wild-type and Bax-deficient mice. Nuclear size was measured from retinal wholemounts. Heterochromatin formation was assessed using transmission electron microscopy, whereas histone H4 acetylation was monitored using immunofluoresence. Ganglion cell and retinal transcript abundance was measured using quantitative PCR. Results. Nuclear and soma sizes linearly correlated in both control and damaged retinas. Cells in wild-type mice exhibited nuclear atrophy within 1 day after optic nerve damage. Three days after crush, nuclear atrophy was restricted to ganglion cells identified by retrograde labeling, while amacrine cells also exhibited some atrophy by 5 days. Similar kinetics of nuclear atrophy were observed in cells deficient for the essential proapoptotic gene Bax. Bax-deficient cells also exhibited other nuclear changes common in wild-type cells, including the deacetylation of histones, formation of heterochromatin, and the silencing of ganglion cell–specific gene expression. Conclusions. Retinal ganglion cell somas and nuclei undergo the AVD in response to optic nerve damage. Atrophy is rapid and precedes the Bax-dependent committed step of the intrinsic apoptotic pathway. PMID:23422829

  4. Pituitary adenoma-neuronal choristoma is a pituitary adenoma with ganglionic differentiation.

    PubMed

    Nguyen, Michaela T; Lavi, Ehud

    2015-12-01

    The presence of ganglion cells within an endocrine pituitary tumor has been named hamartoma, choristoma, gangliocytoma, or most recently pituitary adenoma-neuronal choristoma (PANCH). The presence of neuronal differentiation in regular pituitary adenomas has been previously suggested, however, its origin, the extent of its presence, and the relationship between the neuronal elements and the pituitary adenoma remain uncertain. Thus, to further explore the neuronal potential of pituitary tumors, we used immunohistochemistry on pituitary tumors of different grades, with a neuronal antigen protein (NeuN) antibody as a specific marker for mature neuronal differentiation. We found NeuN expression in 26.47% (9/34) cases of pituitary tumors without ganglionic differentiation (7 adenomas, 1 atypical adenoma and 1 pituitary carcinoma), in addition to NeuN expression in pituitary adenomas with ganglionic cells (2/2). Thus, neuronal expression is an innate property of pituitary adenomas. We propose that the rare presence of ganglionic cells in pituitary adenomas is not the result of a separate lesion or "collision sellar tumors", as previously suggested, but a ganglionic neuronal differentiation in an endocrine neoplasm. The ganglionic cells may be arising from uncommitted stem/progenitor cells that contain both neuronal and endocrine properties. A label of "pituitary adenoma with ganglionic differentiation" would better reflect the dual differentiation in a neuroendocrine tumor than the current label "PANCH".

  5. Oligomeric proanthocyanidin protects retinal ganglion cells against oxidative stress-induced apoptosis.

    PubMed

    Wang, Hui; Zhang, Chanjuan; Lu, Dan; Shu, Xiaoming; Zhu, Lihong; Qi, Renbing; So, Kwok-Fai; Lu, Daxiang; Xu, Ying

    2013-09-01

    The death of retinal ganglion cells is a hallmark of many optic neurodegenerative diseases such as glaucoma and retinopathy. Oxidative stress is one of the major reasons to cause the cell death. Oligomeric proanthocyanidin has many health beneficial effects including antioxidative and neuroprotective actions. Here we tested whether oligomeric proanthocyanidin may protect retinal ganglion cells against oxidative stress induced-apoptosis in vitro. Retinal ganglion cells were treated with hydrogen peroxide with or without oligomeric proanthocyanidin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that treating retinal ganglion cell line RGC-5 cells with 20 μmol/L oligomeric proanthocyanidin significantly decreased the hydrogen peroxide (H2O2) induced death. Results of flow cytometry and Hoechst staining demonstrated that the death of RGC-5 cells was mainly caused by cell apoptosis. We further found that expression of pro-apoptotic Bax and caspase-3 were significantly decreased while anti-apoptotic Bcl-2 was greatly increased in H2O2 damaged RGC-5 cells with oligomeric proanthocyanidin by western blot assay. Furthermore, in retinal explant culture, the number of surviving retinal ganglion cells in H2O2-damaged retinal ganglion cells with oligomeric proanthocyanidin was significantly increased. Our studies thus demonstrate that oligomeric proanthocyanidin can protect oxidative stress-injured retinal ganglion cells by inhibiting apoptotic process.

  6. Short-wavelength cone-opponent retinal ganglion cells in mammals

    PubMed Central

    MARSHAK, DAVID W.; MILLS, STEPHEN L.

    2014-01-01

    In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages. PMID:24759445

  7. Short-wavelength cone-opponent retinal ganglion cells in mammals.

    PubMed

    Marshak, David W; Mills, Stephen L

    2014-03-01

    In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages. PMID:24759445

  8. Hyperactivity of ON-type retinal ganglion cells in streptozotocin-induced diabetic mice.

    PubMed

    Yu, Jun; Wang, Lu; Weng, Shi-Jun; Yang, Xiong-Li; Zhang, Dao-Qi; Zhong, Yong-Mei

    2013-01-01

    Impairment of visual function has been detected in the early stage of diabetes but the underlying neural mechanisms involved are largely unknown. Morphological and functional alterations of retinal ganglion cells, the final output neurons of the vertebrate retina, are thought to be the major cause of visual defects in diabetes but direct evidence to support this notion is limited. In this study we investigated functional changes of retinal ganglion cells in a type 1-like diabetic mouse model. Our results demonstrated that the spontaneous spiking activity of ON-type retinal ganglion cells was increased in streptozotocin-diabetic mice after 3 to 4 months of diabetes. At this stage of diabetes, no apoptotic signals or cell loss were detected in the ganglion cell layer of the retina, suggesting that the functional alterations in ganglion cells occur prior to massive ganglion cell apoptosis. Furthermore, we found that the increased activity of ON-type ganglion cells was mainly a result of reduced inhibitory signaling to the cells in diabetes. This novel mechanism provides insight into how visual function is impaired in diabetic retinopathy. PMID:24069457

  9. The cell stress machinery and retinal degeneration.

    PubMed

    Athanasiou, Dimitra; Aguilà, Monica; Bevilacqua, Dalila; Novoselov, Sergey S; Parfitt, David A; Cheetham, Michael E

    2013-06-27

    Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness. PMID:23684651

  10. Melanopsin containing retinal ganglion cells are light responsive from birth.

    PubMed

    Hannibal, Jens; Fahrenkrug, Jan

    2004-10-25

    Photoentrainment of the biological clock located in the suprachiasmatic nucleus (SCN) begins shortly after birth. Here we show using c-FOS immunoreactivity as a marker for neuronal activity that the melanopsin/PACAP containing retinal ganglion cells (RGCs) which project to the SCN as the retinohypothalamic tract (RHT) are responsive to light from birth. After postnatal day 12 where the classical photoreceptors become functional other RGCs and cells of the inner nuclear cell layer also respond to light. Light also induces c-FOS immunoreactivity in the retinorecipient SCN from the first postnatal day and accordingly PACAP immunoreactive fibres are visible in the SCN. The results indicate that the retina is light responsive before functional rods and cones and that the RHT is functional from birth supporting that photoentrainment of the biological clock begins shortly after birth.

  11. Identification of cone mechanisms in monkey ganglion cells

    PubMed Central

    Gouras, Peter

    1968-01-01

    1. Blue, green, and red sensitive cone mechanisms have been studied in two types of on-centre ganglion cells in the Rhesus monkey's retina. 2. One type of cell receives signals from both green and red sensitive cone mechanisms, both of which excite in the centre and inhibit in the periphery of the cell's receptive field. These cells discharge transiently to maintained stimuli of any wave-length and are called phasic. 3. The second type of cell receives excitatory signals from only one cone mechanism, either blue, green or red sensitive, in the centre, and inhibition from another cone mechanism in the periphery of its receptive field. These cells discharge continuously to maintained stimuli of appropriate wave-length and are called tonic. 4. Tonic cells outnumber phasic cells although both are found adjacent to one another throughout the retina. Phasic cells are relatively more common toward the periphery and tonic cells relatively more common toward the fovea. PMID:4974745

  12. Recent advances in basic research on the trigeminal ganglion.

    PubMed

    Goto, Tetsuya; Oh, Seog Bae; Takeda, Mamoru; Shinoda, Masamichi; Sato, Tadasu; Gunjikake, Kaori K; Iwata, Koichi

    2016-09-01

    Peripheral tissue inflammation can alter the properties of somatic sensory pathways, causing behavioral hypersensitivity and resulting in increased responses to pain caused by noxious stimulation (hyperalgesia) and normally innocuous stimulation (allodynia). These hypersensitivities for nociception are caused by changes in the excitability of trigeminal ganglion (TG) neurons. These changes alter sensory information processing in the neurons in the medullary trigeminal nucleus of caudalis. Increasing information is becoming available regarding trigeminal neuron-neuron/neuron-satellite glial cells (SGCs) communication. The activation of intraganglionic communication plays an important role in the creation and maintenance of trigeminal pathological pain. Therefore, in this review, we focus on the recent findings for sensory functions and pharmacological modulation of TG neurons and SGCs under normal and pathological conditions, and we discuss potential therapeutic targets in glia-neuronal interactions for the prevention of trigeminal neuropathic and inflammatory pain. PMID:27023716

  13. NBQX suppresses inhibitory glycine currents in retinal ganglion cells.

    PubMed

    Yu, W; Miller, R F

    1994-08-15

    The quinoxaline NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline) is a potent non-NMDA receptor antagonist, which appears to be relatively free of antagonistic action at the glycine binding site of the NMDA receptor. However, we report here that at 50 microM, NBQX significantly attenuated the inhibitory currents induced by the exogenous application of 100 microM glycine as observed using whole-cell recordings from ganglion cells in a slice preparation of the tiger salamander retina. In contrast, NBQX had no effect on GABA-mediated inhibition. This observation suggests that care should be taken when attributing the action of NBQX solely to its antagonism of non-NMDA glutamate receptors, particularly when higher concentrations are used.

  14. In Vitro Functional Assessment of Adult Spiral Ganglion Neurons (SGNs).

    PubMed

    Lee, Jeong Han; Sihn, Choongryoul; Wang, Wanging; Flores, Cristina Maria Perez; Yamoah, Ebenezer N

    2016-01-01

    Spiral ganglion neurons (SGNs) faithfully encode acoustic waves from hair cells to the cochlear nucleus (CN) using voltage-dependent ion channels. A sizable portion of our knowledge on SGN functions have been derived from pre-hearing neurons. In post-hearing SGNs, the mechanisms of how they encode the massive sound information without delay and precisely are largely unknown. Mature SGNs are housed in the central bony labyrinth of the cochlea, protected by a well-insulated myelin sheath, making it a technical feat to isolate viable neurons for rigorous functional electrophysiology. Recently, we have overcome the previous intractable hindrance in SGN functional analyses. We provide a step-by-step user-friendly protocol with practical applications, including patch-clamp recordings and imaging by using cultured SGNs. PMID:27259946

  15. Ganglionitis in paraneoplastic subacute sensory neuronopathy: a morphologic study.

    PubMed

    Wanschitz, J; Hainfellner, J A; Kristoferitsch, W; Drlicek, M; Budka, H

    1997-10-01

    A 69-year-old woman presented with subacute sensory neuropathy and autonomic dysfunction of 9 months' duration, associated with high serum titers of anti-Hu antibodies. A small cell carcinoma of the lung was diagnosed by biopsy. She died after cardiorespiratory arrest. At autopsy, spinal and autonomic ganglia showed subacute inflammation with diffuse endoneurial T-cell, B-cell, and plasma cell infiltration. The cytoplasm and nuclei of some ganglion neurons displayed IgG immunocytochemical positivity. CD8+ T cells were tightly attached to, and indented the cell surface of, IgG-positive and IgG-negative neurons. This observation suggests that both cytotoxic T-cell-mediated attack against neurons and humoral mechanisms play a role in paraneoplastic subacute sensory neuronopathy.

  16. Potential Outcome Factors in Subacute Combined Degeneration

    PubMed Central

    Vasconcelos, Olavo M; Poehm, Erika H; McCarter, Robert J; Campbell, William W; Quezado, Zenaide M N

    2006-01-01

    BACKGROUND Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging. PURPOSE To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration. DATA SOURCE We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors. DATA EXTRACTION, SYNTHESIS We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms. RESULTS Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in ≤7 segments and age less than 50 also appear to have higher rates of complete resolution. CONCLUSIONS B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis. PMID:16970556

  17. A Dopamine- and Protein Kinase A-Dependent Mechanism for Network Adaptation in Retinal Ganglion Cells

    PubMed Central

    Vaquero, C. F.; Pignatelli, A.; Partida, G. J.; Ishida, A. T.

    2011-01-01

    Vertebrates can detect light intensity changes in vastly different photic environments, in part, because post-receptoral neurons undergo “network adaptation”. Previous data implicated dopaminergic, cAMP-dependent inhibition of retinal ganglion cells in this process, yet left unclear how this occurs, and whether this occurs in darkness versus light. To test for light- and dopamine-dependent changes in ganglion cell cAMP levels in situ, we immunostained dark- and light-adapted retinas with anti-cAMP antisera, in the presence and absence of various dopamine receptor ligands. To test for direct effects of dopamine receptor ligands and membrane-permeable protein kinase ligands on ganglion cell excitability, we recorded spikes from isolated ganglion cells in perforated-patch whole-cell mode, before and during application of these agents by microperfusion. Our immunostainings show that light, endogenous dopamine, and exogenous dopamine elevate ganglion cell cAMP levels in situ by activating D1-type dopamine receptors. Our spike recordings show that D1-type agonists and 8-bromo cAMP reduce spike frequency and curtail sustained spike firing, and that these effects entail protein kinase A activation. These effects resemble those of background light on ganglion cell responses to light flashes. Network adaptation could thus be produced, to some extent, by dopaminergic modulation of ganglion cell spike generation, a mechanism distinct from modulation of transmitter release onto ganglion cells or of transmitter-gated currents in ganglion cells. Combining these observations, with results obtained in studies of photoreceptor, bipolar, and horizontal cells, indicates that all three layers of neurons in the retina are equipped with mechanisms for adaptation to ambient light. PMID:11606650

  18. Target areas innervated by PACAP-immunoreactive retinal ganglion cells.

    PubMed

    Hannibal, Jens; Fahrenkrug, Jan

    2004-04-01

    The retinohypothalamic tract (RHT) originates from a subset of retinal ganglion cells (RGCs). The cells of the RHT co-store the neurotransmitters PACAP and glutamate, which in a complex interplay mediate light information to the circadian clock located in the suprachiasmatic nuclei (SCN). These ganglion cells are intrinsically photosensitive probably due to expression of melanopsin, a putative photoreceptor involved in light entrainment. In the present study we examined PACAP-containing retinal projections to the brain using intravitreal injection of the anterograde tracer cholera toxin subunit B (ChB) and double immunostaining for PACAP and ChB. Our results show that the PACAP-containing nerve fibres not only constituted the major projections to the SCN and the intergeniculate leaflet of the thalamus but also had a large terminal field in the olivary pretectal nucleus. The contralateral projection dominated except for the SCN, which showed bilateral innervation. PACAP-containing retinal fibres were also found in the ventrolateral preoptic nucleus, the anterior and lateral hypothalamic area, the subparaventricular zone, the ventral part of the lateral geniculate nucleus and the nucleus of the optic tract. Retinal projections not previously described in the rat also contained PACAP. These new projections were found in the lateral posterior nucleus, the posterior limitans nucleus, the dorsal part of the anterior pretectal nucleus and the posterior and medial pretectal nuclei. Only a few PACAP-containing retinal fibres were found in the superior colliculus. Areas innervated by PACAP-immunoreactive fibres also expressed the PACAP-specific PAC1 receptor as shown by in situ hybridization histochemistry. The findings suggest that PACAP plays a role as neurotransmitter in non-imaging photoperception to target areas in the brain regulating circadian timing, masking, regulation of sleep-wake cycle and pupillary reflex.

  19. Petrosal ganglion: a more complex role than originally imagined

    PubMed Central

    Retamal, Mauricio A.; Reyes, Edison P.; Alcayaga, Julio

    2014-01-01

    The petrosal ganglion (PG) is a peripheral sensory ganglion, composed of pseudomonopolar sensory neurons that innervate the posterior third of the tongue and the carotid sinus and body. According to their electrical properties PG neurons can be ascribed to one of two categories: (i) neurons with action potentials presenting an inflection (hump) on its repolarizing phase and (ii) neurons with fast and brisk action potentials. Although there is some correlation between the electrophysiological properties and the sensory modality of the neurons in some species, no general pattern can be easily recognized. On the other hand, petrosal neurons projecting to the carotid body are activated by several transmitters, with acetylcholine and ATP being the most conspicuous in most species. Petrosal neurons are completely surrounded by a multi-cellular sheet of glial (satellite) cells that prevents the formation of chemical or electrical synapses between neurons. Thus, PG neurons are regarded as mere wires that communicate the periphery (i.e., carotid body) and the central nervous system. However, it has been shown that in other sensory ganglia satellite glial cells and their neighboring neurons can interact, partly by the release of chemical neuro-glio transmitters. This intercellular communication can potentially modulate the excitatory status of sensory neurons and thus the afferent discharge. In this mini review, we will briefly summarize the general properties of PG neurons and the current knowledge about the glial-neuron communication in sensory neurons and how this phenomenon could be important in the chemical sensory processing generated in the carotid body. PMID:25538627

  20. Evaluation of new approach to ultrasound guided stellate ganglion block

    PubMed Central

    Ghai, Anju; Kaushik, Teshi; Kundu, Zile Singh; Wadhera, Sarthak; Wadhera, Raman

    2016-01-01

    Background: Ultrasound imaging is an ideal tool for stellate ganglion block (SGB) due to clarity, portability, lack of radiation, and low cost. Ultrasound guided anterior approach requires the application of pressure to the anterior neck and is associated with more risk of injury to inferior thyroid artery, vertebral artery, and esophagus. The lateral approach does not interfere with nerve or vascular structures. Blockade at the C6 vertebral level results in more successful sympathetic blockade of the head and neck with less sympathetic blockade of the upper extremity compared to sympathetic blockade at C7 vertebral level, which produces successful sympathetic blockade of upper extremity. This is helpful in patients of complex regional pain syndrome of the upper limb. Hence, we conducted a study using the lateral approach at C7 level. Materials and Methods: Ultrasound guided SGBs using lateral in-plane technique at C7 level were given in 20 patients suffering from chronic pain patients of upper extremity, head, and neck using 4 ml of 0.25% bupivacaine and 1 ml of 40 mg triamcinolone. The patients were assessed for a numeric pain intensity score (NPIS), the rise in axillary temperature, the range of motion of joints of upper extremity, and resolution of edema at various time intervals up to 3 months. Results: NPIS showed a statistically significant decrease from baseline at 30 min, which was sustained till 3rd month. The rise in axillary temperature after the block was statistically significant, which was sustained till 2nd week. The edema score decreased significantly at all-time intervals (P ≤ 0.001). The restriction of motion in all joints of upper limb decreased from 13 to 3 patients. Conclusion: There is a significant variation in the anatomy of stellate ganglion at the level of C6 and C7. Ultrasound guided lateral approach increases the efficacy of SGB by deposition of drug subfascially with real-time imaging. PMID:27051366

  1. Regional differences in myelination of chick vestibulocochlear ganglion cells.

    PubMed

    Sun, Ying-Jie; Kobayashi, Hiroto; Yoshida, Saori; Shirasawa, Nobuyuki; Naito, Akira

    2013-11-01

    In vertebrates, vestibular and cochlear ganglion (VG and CG, respectively) cells are bipolar neurons with myelinated axons and perikarya. The time course of the myelination of the VG and CG cells during development of chick embryos was investigated. Chick VG and CG from embryonic day at 7-20 (E7-20) were prepared for a transmission electron microscopy, myelin basic protein immunohistochemistry, and real-time quantitative RT-PCR. In the VG cells, myelination was first observed on the peripheral axons of the ampullar nerves at E10, on the utricular and saccular nerves at E12, and on the lagenar and neglecta nerves at E13. In the VG central axons, myelination was first seen on the ampullar nerves at E11, on the utricular and saccular nerves at E13, and on the lagenar nerves at E13. In the CG cells, the myelination was first observed on the peripheral and central axons at E14. In both VG and CG, myelination was observed on the perikarya at E17. These results suggest that the onset of the axonal myelination on the VG cells occurred earlier than that on the CG cells, whereas the perikaryal myelination occurred at about the same time on the both types of ganglion cells. Moreover, the myelination on the ampullar nerves occurred earlier than that on the utricular and saccular nerves. The myelination on the peripheral axons occurred earlier than that on the central axons of the VG cells, whereas that on the central and peripheral axons of the CG cells occurred at about the same time. The regional differences in myelination in relation to the onset of functional activities in the VG and CG cells are discussed.

  2. Adaptation and dynamics of cat retinal ganglion cells.

    PubMed

    Enroth-Cugell, C; Shapley, R M

    1973-09-01

    1. The impulse/quantum (I/Q) ratio was measured as a function of background illumination for rod-dominated, pure central, linear square-wave responses of retinal ganglion cells in the cat.2. The I/Q ratio was constant at low backgrounds (dark adapted state) and inversely proportional to the 0.9 power of the background at high backgrounds (the light adapted state). There was an abrupt transition from the dark-adapted state to the light-adapted state.3. It was possible to define the adaptation level at a particular background as the ratio (I/Q ratio at that background)/(dark adapted I/Q ratio).4. The time course of the square-wave response was correlated with the adaptation level. The response was sustained in the dark-adapted state, partially transient at the transition level, and progressively more transient the lower the impulse/quantum ratio of the ganglion cell became. This was true both for on-centre and off-centre cells.5. The frequency response of the central response mechanism at different adaptation levels was measured. It was a low-pass characteristic in the dark-adapted state and became progressively more of a bandpass characteristic as the cell became more light-adapted.6. The rapidity of onset of adaptation was measured with a time-varying adapting light. The impulse/quantum ratio is reset within 100 msec of the onset of the conditioning light, and is kept at the new value throughout the time the conditioning light is on.7. These results can be explained by a nonlinear feedback model. In the model, it is postulated that the exponential function of the horizontal cell potential controls transmission from rods to bipolars. This model has an abrupt transition from dark- to light-adapted states, and its response dynamics are correlated with adaptation level.

  3. Phase diagram of degenerate exciton systems.

    PubMed

    Lai, C W; Zoch, J; Gossard, A C; Chemla, D S

    2004-01-23

    Degenerate exciton systems have been produced in quasi-two-dimensional confined areas in semiconductor coupled quantum well structures. We observed contractions of clouds containing tens of thousands of excitons within areas as small as (10 micron)2 near 10 kelvin. The spatial and energy distributions of optically active excitons were determined by measuring photoluminescence as a function of temperature and laser excitation and were used as thermodynamic quantities to construct the phase diagram of the exciton system, which demonstrates the existence of distinct phases. Understanding the formation mechanisms of these degenerate exciton systems can open new opportunities for the realization of Bose-Einstein condensation in the solid state.

  4. Visual system degeneration induced by blast overpressure.

    PubMed

    Petras, J M; Bauman, R A; Elsayed, N M

    1997-07-25

    The effect of blast overpressure on visual system pathology was studied in 14 male Sprague-Dawley rats weighing 360-432 g. Blast overpressure was simulated using a compressed-air driven shock tube, with the aim of studying a range of overpressures causing sublethal injury. Neither control (unexposed) rats nor rats exposed to 83 kiloPascals (kPa) overpressure showed evidence of visual system pathology. Neurological injury to brain visual pathways was observed in male rats surviving blast overpressure exposures of 104-110 kPa and 129-173 kPa. Optic nerve fiber degeneration was ipsilateral to the blast pressure wave. The optic chiasm contained small numbers of degenerated fibers. Optic tract fiber degeneration was present bilaterally, but was predominantly ipsilateral. Optic tract fiber degeneration was followed to nuclear groups at the level of the midbrain, midbrain-diencephalic junction, and the thalamus where degenerated fibers arborized among the neurons of: (i) the superior colliculus, (ii) pretectal region, and (iii) the lateral geniculate body. The superior colliculus contained fiber degeneration localized principally to two superficial layers (i) the stratum opticum (layer III) and (ii) stratum cinereum (layer II). The pretectal area contained degenerated fibers which were widespread in (i) the nucleus of the optic tract, (ii) olivary pretectal nucleus, (iii) anterior pretectal nucleus, and (iv) the posterior pretectal nucleus. Degenerated fibers in the lateral geniculate body were not universally distributed. They appeared to arborize among neurons of the dorsal and ventral nuclei: the ventral lateral geniculate nucleus (parvocellular and magnocellular parts); and the dorsal lateral geniculate nucleus. The axonopathy observed in the central visual pathways and nuclei of the rat brain are consistent with the presence of blast overpressure induced injury to the retina. The orbital cavities of the human skull contain frontally-directed eyeballs for binocular

  5. Pathogenesis of tendinopathies: inflammation or degeneration?

    PubMed Central

    Abate, Michele; Gravare-Silbernagel, Karin; Siljeholm, Carl; Di Iorio, Angelo; De Amicis, Daniele; Salini, Vincenzo; Werner, Suzanne; Paganelli, Roberto

    2009-01-01

    The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. PMID:19591655

  6. Retinal Cell Degeneration in Animal Models

    PubMed Central

    Niwa, Masayuki; Aoki, Hitomi; Hirata, Akihiro; Tomita, Hiroyuki; Green, Paul G.; Hara, Akira

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. PMID:26784179

  7. [Degenerated papillomatosis of the bile duct].

    PubMed

    De Castro Gutiérrez, J; Armengol Carrasco, M; Oller Sales, B; Fdez-Llamazares Rodríguez, J; Julián Ibáñez, J F; Broggi Trías, M A; Salvá Lacombe, J A

    1989-07-01

    Papillomatosis of the biliary ducts is exceptional. It is defined by the presence of multiple, benign, papillary type, epithelial tumors on the choledochus and hepatic ducts, and can also effect the gallbladder and intrahepatic bile ducts. It courses with a tendency to recurrence and secondary degeneration, and its prognosis is uncertain and sometimes grave. The treatment is surgical and depends on the extension of the lesions, often being only palliative. The techniques of choice are curettage and biliodigestive derivation. A case is presented of degenerated papillomatosis treated by cephalic duodenopancreatectomy and cholecystectomy.

  8. Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity.

    PubMed

    Yamauchi, Mika; Tsuruma, Kazuhiro; Imai, Shunsuke; Nakanishi, Tomohiro; Umigai, Naofumi; Shimazawa, Masamitsu; Hara, Hideaki

    2011-01-10

    Crocetin is a carotenoid that is the aglicone of crocin, which are found in saffron stigmas (Crocus sativus L.) and gardenia fruit (Gardenia jasminoides Ellis). In this study, we investigated the effects of crocetin on retinal damage. To examine whether crocetin affects stress pathways, we investigated intracellular oxidation induced by reactive oxygen species, expression of endoplasmic reticulum (ER) stress-related proteins, disruption of the mitochondrial membrane potential (ΔΨ(m)), and caspases activation. In vitro, we employed cultured retinal ganglion cells (RGC-5, a mouse ganglion cell-line transformed using E1A virus). Cell damage was induced by tunicamycin or hydrogen peroxide (H(2)O(2)) exposure. Crocetin at a concentration of 3μM showed the inhibitory effect of 50-60% against tunicamycin- and H(2)O(2)-induced cell death and inhibited increase in caspase-3 and -9 activity. Moreover, crocetin inhibited the enzymatic activity of caspase-9 in a cell-free system. In vivo, retinal damage in mice was induced by exposure to white light at 8000lx for 3h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5days after light exposure and recording the electroretinogram (ERG). Retinal cell damage was also detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at 48h after light exposure. Crocetin at 100mg/kg, p.o. significantly inhibited photoreceptor degeneration and retinal dysfunction and halved the expression of TUNEL-positive cells. These results indicate that crocetin has protective effects against retinal damage in vitro and in vivo, suggesting that the mechanism may inhibit increase in caspase-3 and -9 activities after retinal damage. PMID:20951131

  9. Ganglion cyst and olecranon physis nonunion in a baseball pitcher: unique treatment after conservative therapy fails.

    PubMed

    Burman, Mark L; Aljassir, Fawzi; Coughlin, Larry P

    2004-06-01

    Although ganglion cysts and stress fractures occur at many joints, the presence of both disorders at the same joint is rare. In this unusual case, a 30-year-old professional pitcher had been treated conservatively for presumed olecranon bursitis in his right (throwing) arm, but, when therapy failed, he sought additional care. A thorough workup and subsequent surgery revealed a ganglion cyst and nonunion of a stress fracture of the olecranon physis. The ganglion cyst had its origin at the fracture site, and both cyst and bone fragment were excised. The patient had a full recovery and was able to resume pitching as an instructor 18 months after surgery.

  10. GABAergic and glycinergic pathways to goldfish retinal ganglion cells: an ultrastructural double label study

    SciTech Connect

    Muller, J.F.

    1987-01-01

    An ultrastructural double label has been employed to compare GABAergic and glycinergic systems in the inner plexiform layer (IPL) of the goldfish retina. Electron microscope autoradiography of /sup 3/H-GABA and /sup 3/H-glycine uptake was combined with retrograde HRP-labeling of ganglion cells. When surveyed for distribution, GABAergic and glycinergic synapses were found onto labeled ganglion cells throughout the IPL. This reinforces previous physiological work that described GABAergic and glycinergic influences on a variety of ganglion cells in goldfish and carp; These physiological effects often reflect direct inputs.

  11. Spinal nerve root ganglionitis as a cause of disc herniation: case report.

    PubMed

    Roser, Florian; Ritz, Rainer; Morgalla, Matthias; Tatagiba, Marcos; Bornemann, Antje

    2005-04-01

    The authors report on a patient in whom monoradicular pain was caused by ganglionitis of a spinal nerve. Neuroimaging and intraoperative findings identified what were thought to be tumorlike changes in the affected nerve root. The neuropathological examination, however, revealed typical signs of ganglionitis. This rare inflammation usually appears with viral infections, as part of paraneoplastic symptoms, or in the presence of Sjögren disease. Because all of these differential diagnoses were negative in the treated patient, chronic nerve root compression due to disc herniation was suspected as the causative factor for the spinal ganglionitis.

  12. Immunohistochemical study of the neuropeptides in the stellate ganglion of the water buffalo.

    PubMed

    Nasu, T; De Ocampo, G; Molina, H A; Tateyama, S; Morimoto, M

    2000-05-01

    The localization of some neuropeptides including neuropeptide Y (NPY), substance P (SP), calcitonin gene related peptide (CGRP), vasoactive intestinal peptide (VIP), galanin (Gal), methionine enkephalin (M-ENK), tyrosine hydroxylase (TH) immunoreactivity was studied in the stellate ganglion (SG) of water buffalo. NPY, SP, Gal and TH immunoreactivities were present in almost all of the ganglion cells. NPY, SP, Gal, SP, CGRP, VIP and M-ENK immunoreactive nerve fibers were also seen in the SG. The localization and pattern of distribution of these peptides in the water buffalo stellate ganglion were compared with those in stellate ganglia of other mammalian species.

  13. [Optogenetics and prosthetic treatment of retinal degeneration].

    PubMed

    Kirpichnikov, M P; Ostrovskiy, M A

    2015-01-01

    This is a review of the current state of optogenetics-based research in the field of ophthalmology and physiology of vision. Optogenetics employs an interdisciplinary approach that amalgamates gene engineering, optics, and physiology. It involves exogenous expression of a light-activated protein in a very particular retinal cell enabling regulation (stimulation vs. inhibition) of its physiological activity. The experience with gene therapy came in very useful for optogenetics. However, unlike gene therapy, which is aimed at repairing damaged genes or replacing them with healthy ones, optogenetics is focused on protein genes delivery for further molecular control of the cell. In retina, the loss of photoreceptors is not necessarily followed by neuronal loss (at least ganglion cells remain intact), which determines the practicability of prosthetic treatment. Clinical trials can now be considered, owing to the first successful conversion of ganglion cells of mouse degenerative retinas into artificial photoreceptive cells with ON and OFF receptive fields, which is crucial for spatial vision. The following issues are reviewed here in detail: 1. Choice of cell targets within the degenerative retina. 2. Strategy of utilizing the existing light-sensitive agents and development of new optogenetic tools. 3. Gene delivery and expression in retinal cells. 4. Methods of evaluating the treatment success. 5. Selection criteria for optogenetic prosthetics. The conclusion discusses currently unsolved problems and prospects for optogenetic approaches to retinal prosthetics.

  14. Protective Effect of Total Flavones from Hippophae rhamnoides L. against Visible Light-Induced Retinal Degeneration in Pigmented Rabbits.

    PubMed

    Wang, Yong; Huang, Fenghong; Zhao, Liang; Zhang, Di; Wang, Ou; Guo, Xiaoxuan; Lu, Feng; Yang, Xue; Ji, Baoping; Deng, Qianchun

    2016-01-13

    Sea buckthorn (Hippophae rhamnoides L.) flavones have been used as candidate functional food ingredients because of their bioactivities, such as treating cardiovascular disorders, lowering plasma cholesterol level, and regulating immune function. However, the protective effects of sea buckthorn flavones against retinal degeneration remain unclear to date. This study investigated the protective effects of total flavones from H. rhamnoides (TFH) against visible light-induced retinal damage and explored the related mechanisms in pigmented rabbits. Rabbits were treated with TFH (250 and 500 mg/kg) for 2 weeks pre-illumination and 1 week post-illumination until sacrifice. Retinal function was quantified by performing electroretinography 1 day before and 1, 3, and 7 days after light exposure (18000 lx for 2 h). Retinal degeneration was evaluated by measuring the thickness of the outer nuclear layer (ONL) and performing the TUNEL assay 7 days after light exposure. Enzyme-linked immunosorbent assay, Western blot analysis, and immunohistochemistry were used to explore the antioxidant, anti-inflammatory, and anti-apoptotic mechanisms of TFH during visible light-induced retinal degeneration. Light exposure produced a degenerative effect primarily on the ONL, inner nuclear layer (INL), and ganglion cell layer (GCL). TFH significantly attenuated the destruction of electroretinograms caused by light damage, maintained ONL thickness, and decreased the number of TUNEL-positive cells in the INL and GCL. TFH ameliorated the retinal oxidative stress (GSH-Px, CAT, T-AOC, and MDA), inflammation (IL-1β and IL-6), angiogenesis (VEGF), and apoptosis (Bax, Bcl2, and caspase-3) induced by light exposure. Therefore, TFH exhibited protective effects against light-induced retinal degeneration by increasing the antioxidant defense mechanisms, suppressing pro-inflammatory and angiogenic cytokines, and inhibiting retinal cell apoptosis. PMID:26653970

  15. Protective Effect of Total Flavones from Hippophae rhamnoides L. against Visible Light-Induced Retinal Degeneration in Pigmented Rabbits.

    PubMed

    Wang, Yong; Huang, Fenghong; Zhao, Liang; Zhang, Di; Wang, Ou; Guo, Xiaoxuan; Lu, Feng; Yang, Xue; Ji, Baoping; Deng, Qianchun

    2016-01-13

    Sea buckthorn (Hippophae rhamnoides L.) flavones have been used as candidate functional food ingredients because of their bioactivities, such as treating cardiovascular disorders, lowering plasma cholesterol level, and regulating immune function. However, the protective effects of sea buckthorn flavones against retinal degeneration remain unclear to date. This study investigated the protective effects of total flavones from H. rhamnoides (TFH) against visible light-induced retinal damage and explored the related mechanisms in pigmented rabbits. Rabbits were treated with TFH (250 and 500 mg/kg) for 2 weeks pre-illumination and 1 week post-illumination until sacrifice. Retinal function was quantified by performing electroretinography 1 day before and 1, 3, and 7 days after light exposure (18000 lx for 2 h). Retinal degeneration was evaluated by measuring the thickness of the outer nuclear layer (ONL) and performing the TUNEL assay 7 days after light exposure. Enzyme-linked immunosorbent assay, Western blot analysis, and immunohistochemistry were used to explore the antioxidant, anti-inflammatory, and anti-apoptotic mechanisms of TFH during visible light-induced retinal degeneration. Light exposure produced a degenerative effect primarily on the ONL, inner nuclear layer (INL), and ganglion cell layer (GCL). TFH significantly attenuated the destruction of electroretinograms caused by light damage, maintained ONL thickness, and decreased the number of TUNEL-positive cells in the INL and GCL. TFH ameliorated the retinal oxidative stress (GSH-Px, CAT, T-AOC, and MDA), inflammation (IL-1β and IL-6), angiogenesis (VEGF), and apoptosis (Bax, Bcl2, and caspase-3) induced by light exposure. Therefore, TFH exhibited protective effects against light-induced retinal degeneration by increasing the antioxidant defense mechanisms, suppressing pro-inflammatory and angiogenic cytokines, and inhibiting retinal cell apoptosis.

  16. Assessment of inner retina dysfunction and progressive ganglion cell loss in a mouse model of glaucoma.

    PubMed

    Pérez de Lara, María J; Santano, Concepción; Guzmán-Aránguez, Ana; Valiente-Soriano, F Javier; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; de la Villa, Pedro; Pintor, Jesús

    2014-05-01

    The DBA/2J mouse is a model of ocular hypertension and retinal ganglion cell (RGC) degeneration, the main features of which are iris pigment dispersion (IPD) and iris stromal atrophy (ISA). These animals also experience glaucomatous changes, including an increase in intraocular pressure (IOP) beginning at about 9-12 months of age and sectorial RGC death in the retina. The aim of this study was to determine the onset of functional changes exhibited by DBA/2J mice in the inner retina. This was performed by means of electroretinographic recordings (scotopic threshold response, STR) and their correlation with morphological changes (loss of RGCs). To this end, we recorded the scotopic threshold response in control C57BL/6J and in DBA/2J mice at different ages. The RGCs, in both DBA/2J and C57BL/6J animals, were identified at 15 months of age by retrograde tracing with an analogue of fluorogold, hydroxystilbamidine methanesulfonate (OHSt), applied on the superior colliculi. Whole mount retinas were processed to quantify the population of RGCs identified by fluorogold tracing and Brn3a immunodetection, and were counted using image analysis software; an isodensity contour plot was generated for each retina. DBA/2J mice showed a significant reduction in the positive STR (pSTR) amplitudes at 12 months of age, as compared to control C57BL/6J mice of the same age. The pSTR mean amplitude decreased to approximately 27.82% of the values recorded in control mice (p = 0.0058). STR responses decreased in both strains as a result of the natural process of aging, but the decrease was more pronounced in DBA/2J mice. Furthermore, quantification of the total number of RGCs identified by OHSt and Brn3a expression showed a reduced population of RGCs in DBA/2J mice as compared to control mice. Regression analysis revealed significant correlations between the decrease in pSTR and a non-homogeneous reduction in the number of RGCs throughout the retina. Our results indicate the existence of

  17. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  18. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  19. The nature of apraxia in corticobasal degeneration.

    PubMed Central

    Leiguarda, R; Lees, A J; Merello, M; Starkstein, S; Marsden, C D

    1994-01-01

    Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia and movement imitation, four on tests of sequential arm movements (all of whom had ideomotor apraxia), and three on tests of ideational apraxia (all of whom had ideomotor apraxia). Ideomotor apraxia significantly correlated with deficit in both the mini mental state examination and in a task sensitive to frontal lobe dysfunction (picture arrangement). Two of the three patients with ideomotor apraxia and ideational apraxia showed severe cognitive impairments. The alien limb behaviour was present only in patients with ideomotor apraxia. In conclusion, ideomotor apraxia is the most frequent type of apraxia in corticobasal degeneration, and may be due to dysfunction of the supplementary motor area. There is a subgroup of patients with corticobasal degeneration who have a severe apraxia (ideomotor and ideational apraxia), which correlates with global cognitive impairment, and may result from additional parietal or diffuse cortical damage. PMID:8163995

  20. On abstract degenerate neutral differential equations

    NASA Astrophysics Data System (ADS)

    Hernández, Eduardo; O'Regan, Donal

    2016-10-01

    We introduce a new abstract model of functional differential equations, which we call abstract degenerate neutral differential equations, and we study the existence of strict solutions. The class of problems and the technical approach introduced in this paper allow us to generalize and extend recent results on abstract neutral differential equations. Some examples on nonlinear partial neutral differential equations are presented.

  1. Spectroscopic observations of cool degenerate star candidates

    NASA Technical Reports Server (NTRS)

    Hintzen, P.

    1986-01-01

    Spectroscopic observations are reported for 23 Luyten Half-Second degenerate star candidates and for 13 Luyten-Palomar common proper-motion pairs containing possible degenerate star components. Twenty-five degenerate stars are identified, 20 of which lack previous spectroscopy. Most of these stars are cool - Luyten color class g or later. One star, LP 77-57, shows broad continuum depressions similar to those in LHS 1126, which Liebert and Dahn attributed to pressure-shifted C2. A second degenerate star, LHS 290, exhibits apparent strong Swan bands which are blueshifted about 75 A. Further observations, including polarimetry and photometry, are required to appraise the spectroscopic peculiarities of these stars. Finally, five cool, sharp-lined DA white dwarfs have been observed to detect lines of metals and to determine line strengths. None of these DAs show signs of Mg b or the G band, and four show no evidence of Ca II K. The attempt to detect Ca MI in the fifth star, G199-71, was inconclusive.

  2. Pudendal Nerve Entrapment Syndrome due to a Ganglion Cyst: A Case Report.

    PubMed

    Lee, Jae Wook; Lee, Sung-Moon; Lee, Dong Gyu

    2016-08-01

    Pudendal nerve entrapment syndrome is an unusual cause of chronic pelvic pain. We experienced a case of pudendal neuralgia associated with a ganglion cyst. A 60-year-old male patient with a tingling sensation and burning pain in the right buttock and perineal area visited our outpatient rehabilitation center. Pelvis magnetic resonance imaging showed the presence of multiple ganglion cysts around the right ischial spine and sacrospinous ligament, and the pudendal nerve and vessel bundle were located between the ischial spine and ganglion cyst at the entrance of Alcock's canal. We aspirated the lesions under ultrasound guidance, and consequently his symptoms subsided during a 6-month follow-up. This is the first report of pudendal neuralgia caused by compression from a ganglion cyst around the sacrospinous ligament. PMID:27606282

  3. Pudendal Nerve Entrapment Syndrome due to a Ganglion Cyst: A Case Report

    PubMed Central

    2016-01-01

    Pudendal nerve entrapment syndrome is an unusual cause of chronic pelvic pain. We experienced a case of pudendal neuralgia associated with a ganglion cyst. A 60-year-old male patient with a tingling sensation and burning pain in the right buttock and perineal area visited our outpatient rehabilitation center. Pelvis magnetic resonance imaging showed the presence of multiple ganglion cysts around the right ischial spine and sacrospinous ligament, and the pudendal nerve and vessel bundle were located between the ischial spine and ganglion cyst at the entrance of Alcock's canal. We aspirated the lesions under ultrasound guidance, and consequently his symptoms subsided during a 6-month follow-up. This is the first report of pudendal neuralgia caused by compression from a ganglion cyst around the sacrospinous ligament. PMID:27606282

  4. Large Ganglion Cyst with Unusual Location on the Back—A Case Report

    PubMed Central

    Nielsen, Thomas Wagner; Berg, Jais Oliver

    2016-01-01

    Summary: A ganglion cyst is a soft tissue tumor-like lesion filled with colloid material commonly located on the hand and wrist. We report a case of a large ganglion cyst with an unusual location on the back. The patient presented with a mass growing over 2 months measuring 11.2 × 4.7 × 7.2 cm on magnetic resonance imaging. Ultrasound and puncture was attempted twice without achieving drainage. After surgical removal, histologic examination diagnosed the tumor as a ganglion cyst. We conclude that when evaluating a subcutaneous soft tissue mass, regardless of localization, a ganglion cyst may be a differential diagnosis. PMID:27482477

  5. Compression of the palmar cutaneous nerve by ganglions of the wrist.

    PubMed

    Gessini, L; Jandolo, B; Pietrangeli, A; Senese, A

    1983-01-01

    Two cases of compression of the palmar cutaneous nerve by ganglion of the wrist are presented. The anatomy of the region, compression factors, mechanism and clinical features are discussed. Timely surgical removal of compression is recommended.

  6. The inflammatory reaction of paraneoplastic ganglionitis and encephalitis: an immunohistochemical study.

    PubMed

    Panegyres, P K; Reading, M C; Esiri, M M

    1993-02-01

    To elucidate the cellular mechanisms of tissue injury in paraneoplastic states, tissues from two patients with small cell carcinoma of the lung and paraneoplastic neurological syndromes were studied. One patient had encephalitis with ganglionitis, and the other ganglionitis. Immunocytochemistry on brain and ganglia was performed using monoclonal and polyclonal antibodies. The majority of the inflammatory cells in brain and ganglia were T-cells, of both helper and cytotoxic subtypes. There were more macrophages in the inflammatory infiltrate of ganglia than in the brain of encephalitis. Major histocompatibility complex class I and II antigen expression was greater in the mononuclear cells in brain than in ganglia. There was no evidence of complement deposition and little evidence for antibody synthesizing cells. Our findings suggest a T-cell-mediated immune attack in paraneoplastic ganglionitis and encephalitis, with a greater role for macrophages in ganglionitis.

  7. Herpes simplex virus vaccine: protection from stomatitis, ganglionitis, encephalitis and latency.

    PubMed

    Kitces, E N; Payne, W J; Morahan, P S; Tew, J G; Murray, B K

    1978-01-01

    A mouse model system was developed for studying the pathogenesis of oral infection with herpes simplex virus type 1 and the protection offered by prior immunization with a nucleic acid-free vaccine. Of non-immunized mice, 95-100% developed ulcerative lesions 3-5 days following application of virus to abraded oral epithelial surfaces. Infection of the ipsilateral sensory (trigeminal) ganglion and the cerebellum occurred by day 2 and sequentially progressed to the contralateral ganglion by day 4 and to the cerebrum by day 5. Prior immunization of mice with an inactivated virus vaccine, and most importantly, with a vaccine free of nucleic acid, protected mice from subsequent oral virus infection. Protection was demonstrated by: (i) reduction in the incidence and severity of primary oral lesions; (ii) a decrease in the number of mice with acute ganglionic infection or dying of encephalitis; and (iii) a reduction in the incidence of latent trigeminal ganglionic infection.

  8. Pudendal Nerve Entrapment Syndrome due to a Ganglion Cyst: A Case Report

    PubMed Central

    2016-01-01

    Pudendal nerve entrapment syndrome is an unusual cause of chronic pelvic pain. We experienced a case of pudendal neuralgia associated with a ganglion cyst. A 60-year-old male patient with a tingling sensation and burning pain in the right buttock and perineal area visited our outpatient rehabilitation center. Pelvis magnetic resonance imaging showed the presence of multiple ganglion cysts around the right ischial spine and sacrospinous ligament, and the pudendal nerve and vessel bundle were located between the ischial spine and ganglion cyst at the entrance of Alcock's canal. We aspirated the lesions under ultrasound guidance, and consequently his symptoms subsided during a 6-month follow-up. This is the first report of pudendal neuralgia caused by compression from a ganglion cyst around the sacrospinous ligament.

  9. Expression of ghrelin in human fetal adrenal glands and paraadrenal nerve ganglions.

    PubMed

    Obara-Moszyńska, Monika; Kedzia, Andrzej; Chmielnicka-Kopaczyk, Maria

    2009-01-01

    The aim of this paper was assessment of location, expression and role of ghrelin in the development and maturation of human fetal adrenal glands and paraadrenal nerve ganglions. Immunohistochemistry was used. The strongest expression of ghrelin was detected in the fetal zone of the adrenal glands, in the neuroepithelial cells of the medullar portion of the adrenals and in few nerve ganglion cells. Ghrelin takes part in molecular processes of proliferation and maturation, and does not influence on steroidogenesis.

  10. Intraosseous Ganglion of the Distal Tibia: Clinical, Radiological, and Operative Management

    PubMed Central

    Sedeek, Sedeek Mohamed; Choudry, Q.; Garg, S.

    2015-01-01

    Intraosseous ganglia are benign cystic lesions located in the subchondral bone. Intraosseous ganglion cysts of the ankle are relatively uncommon. We present a case of recurrent intraosseous ganglion in the ankle of a 41-year-old female who had recurrence after initial surgery. She was treated effectively by curettage and autogenous cancellous bone grafting. At the final follow-up, satisfactory results were obtained with no recurrence or complications. PMID:25664195

  11. Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance

    PubMed Central

    Manuel, Martine; Pratt, Thomas; Liu, Min; Jeffery, Glen; Price, David J

    2008-01-01

    Background The transcription factor Pax6 is expressed by many cell types in the developing eye. Eyes do not form in homozygous loss-of-function mouse mutants (Pax6Sey/Sey) and are abnormally small in Pax6Sey/+ mutants. Eyes are also abnormally small in PAX77 mice expressing multiple copies of human PAX6 in addition to endogenous Pax6; protein sequences are identical in the two species. The developmental events that lead to microphthalmia in PAX77 mice are not well-characterised, so it is not clear whether over- and under-expression of Pax6/PAX6 cause microphthalmia through similar mechanisms. Here, we examined the consequences of over-expression for the eye and its axonal connections. Results Eyes form in PAX77+/+ embryos but subsequently degenerate. At E12.5, we found no abnormalities in ocular morphology, retinal cell cycle parameters and the incidence of retinal cell death. From E14.5 on, we observed malformations of the optic disc. From E16.5 into postnatal life there is progressively more severe retinal dysplasia and microphthalmia. Analyses of patterns of gene expression indicated that PAX77+/+ retinae produce a normal range of cell types, including retinal ganglion cells (RGCs). At E14.5 and E16.5, quantitative RT-PCR with probes for a range of molecules associated with retinal development showed only one significant change: a slight reduction in levels of mRNA encoding the secreted morphogen Shh at E16.5. At E16.5, tract-tracing with carbocyanine dyes in PAX77+/+ embryos revealed errors in intraretinal navigation by RGC axons, a decrease in the number of RGC axons reaching the thalamus and an increase in the proportion of ipsilateral projections among those RGC axons that do reach the thalamus. A survey of embryos with different Pax6/PAX6 gene dosage (Pax6Sey/+, Pax6+/+, PAX77+ and PAX77+/+) showed that (1) the total number of RGC axons projected by the retina and (2) the proportions that are sorted into the ipsilateral and contralateral optic tracts at the

  12. Age-related Hearing Loss: GABA, Nicotinic Acetylcholine and NMDA Receptor Expression Changes in Spiral Ganglion Neurons of the Mouse

    PubMed Central

    Tang, Xiaolan; Zhu, Xiaoxia; Ding, Bo; Walton, Joseph P.; Frisina, Robert D.; Su, Jiping

    2014-01-01

    Age-related hearing loss – presbycusis – is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate gamma-amino butyric acid A (GABAA) receptor subunit α1, nicotinic acetylcholine (nACh) receptor subunit β2, and N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative RT-PCR techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40 dB from 3–48 kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40 dB from 6–49 kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. Spiral ganglion neuron (SGN) density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1 amplitude. mRNA and protein expression of GABAAR α1 and AChR β2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss. PMID:24316061

  13. Anti-dorsal root ganglion neuron antibody in a case of dorsal root ganglionitis associated with Sjögren's syndrome.

    PubMed

    Satake, M; Yoshimura, T; Iwaki, T; Yamada, T; Kobayashi, T

    1995-10-01

    We report the case of a 59-year-old woman with primary Sjögren's syndrome who developed hypesthesia, hypalgesia, and neurogenic arthropathy in her lower limbs. Neurological examination and electrophysiological studies indicated involvement of the dorsal root ganglia. The immunohistochemistry of sections of rat dorsal root ganglion (DRG) showed that the IgG in the serum and cerebrospinal fluid (CSF) from the patient bound to the neuronal perikarya of small DRG neurons but not to the cerebellum or peripheral nerves. These results, consistent with particular impairment of pain and touch senses, suggest that dorsal root ganglionitis in primary Sjögren's syndrome is mediated by humoral autoimmunity.

  14. Pilot evaluation of a stellate ganglion block for the treatment of hot flashes

    PubMed Central

    Pachman, Deirdre R.; Barton, Debra; Carns, Paul E.; Novotny, Paul J.; Wolf, Sherry; Linquist, Breanna; Kohli, Sadhna; Smith, DeAnne R.; Loprinzi, Charles L.

    2011-01-01

    Purpose Hot flashes are a significant problem in breast cancer patients, especially because the most effective therapy, estrogen, is often contraindicated. Based on recent pilot data from a single group supporting the use of a stellate ganglion block for the treatment of hot flashes, the present pilot trial was done to further evaluate the hypothesis that a stellate ganglion block may be a safe and effective therapy for hot flashes. Methods In women with breast cancer who had hot flashes, a stellate ganglion block was performed after 1 week of baseline hot flash data collection. The main efficacy measures were the changes from baseline in hot flash frequency and hot flash score during the 6th week. Results Ten patients were enrolled between 4/23/2009 and 7/10/2009; eight patients were evaluable. After the stellate ganglion block, the mean hot flash frequency and score decreased from baseline values by over 60% during some of the post-treatment weeks. The mean hot flash frequency and score at week 6 decreased from baseline values by 44% and 45%, respectively. There were no significant adverse events clearly attributed to the stellate ganglion blocks. Conclusions The results of this pilot trial support that stellate ganglion blocks may be a helpful therapy for hot flashes. A prospective placebo-controlled clinical trial should be done to more definitively determine this contention. PMID:20496155

  15. Cell type-specific bipolar cell input to ganglion cells in the mouse retina.

    PubMed

    Neumann, S; Hüser, L; Ondreka, K; Auler, N; Haverkamp, S

    2016-03-01

    Many distinct ganglion cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion cell types in the mouse retina receive selective input from specific bipolar cell types or if they sample their synaptic input non-selectively from all bipolar cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 bipolar cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion cell types, which co-stratified with type 2 bipolar cells and assessed the total number of bipolar input synapses and the proportion of synapses deriving from type 2 bipolar cells. Only JAM-B ganglion cells received synaptic input preferentially from bipolar cell types other than type 2 bipolar cells whereas the other analyzed ganglion cell types sampled their bipolar input most likely from all bipolar cell terminals within their dendritic arbor.

  16. Broad Thorny Ganglion Cells: A Candidate for Visual Pursuit Error Signaling in the Primate Retina

    PubMed Central

    Manookin, Michael B.; Neitz, Jay; Rieke, Fred

    2015-01-01

    Functional analyses exist only for a few of the morphologically described primate ganglion cell types, and their correlates in other mammalian species remain elusive. Here, we recorded light responses of broad thorny cells in the whole-mounted macaque retina. They showed ON-OFF-center light responses that were strongly suppressed by stimulation of the receptive field surround. Spike responses were delayed compared with parasol ganglion cells and other ON-OFF cells, including recursive bistratified ganglion cells and A1 amacrine cells. The receptive field structure was shaped by direct excitatory synaptic input and strong presynaptic and postsynaptic inhibition in both ON and OFF pathways. The cells responded strongly to dark or bright stimuli moving either in or out of the receptive field, independent of the direction of motion. However, they did not show a maintained spike response either to a uniform background or to a drifting plaid pattern. These properties could be ideally suited for guiding movements involved in visual pursuit. The functional characteristics reported here permit the first direct cross-species comparison of putative homologous ganglion cell types. Based on morphological similarities, broad thorny ganglion cells have been proposed to be homologs of rabbit local edge detector ganglion cells, but we now show that the two cells have quite distinct physiological properties. Thus, our data argue against broad thorny cells as the homologs of local edge detector cells. PMID:25834063

  17. Curcumin Attenuates Staurosporine-Mediated Death of Retinal Ganglion Cells

    PubMed Central

    Burugula, Balabharathi; Ganesh, Bhagyalaxmi S.

    2011-01-01

    Purpose. Staurosporine (SS) causes retinal ganglion cell (RGC) death in vivo, but the underlying mechanisms have been unclear. Since previous studies on RGC-5 cells indicated that SS induces cell death by elevating proteases, this study was undertaken to investigate whether SS induces RGC loss by elevating proteases in the retina, and curcumin prevents SS-mediated death of RGCs. Methods. Transformed mouse retinal ganglion-like cells (RGC-5) were treated with 2.0 μM SS and various doses of curcumin. Two optimal doses of SS (12.5 and 100 nM) and curcumin (2.5 and 10 μM) were injected into the vitreous of C57BL/6 mice. Matrix metalloproteinase (MMP)-9, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) activities were assessed by zymography assays. Viability of RGC-5 cells was assessed by MTT assays. RGC and amacrine cell loss in vivo was assessed by immunostaining with Brn3a and ChAT antibodies, respectively. Frozen retinal cross sections were immunostained for nuclear factor-κB (NF-κB). Results. Staurosporine induced uPA and tPA levels in RGC-5 cells, and MMP-9, uPA, and tPA levels in the retinas and promoted the death of RGC-5 cells in vitro and RGCs and amacrine cells in vivo. In contrast, curcumin attenuated RGC and amacrine cell loss, despite elevated levels of proteases. An NF-κB inhibitory peptide reversed curcumin-mediated protective effect on RGC-5 cells, but did not inhibit protease levels. Curcumin did not inhibit protease levels in vivo, but attenuated RGC and amacrine cell loss by restoring NF-κB expression. Conclusions. The results show that curcumin attenuates RGC and amacrine cell death despite elevated levels of proteases and raises the possibility that it may be used as a plausible adjuvant therapeutic agent to prevent the loss of these cells in retinal degenerative conditions. PMID:21498608

  18. Photovoltaic restoration of sight with high visual acuity in rats with retinal degeneration

    NASA Astrophysics Data System (ADS)

    Palanker, D.; Goetz, G.; Lorach, H.; Mandel, Y.; Smith, R.; Boinagrov, D.; Lei, X.; Kamins, T.; Harris, J.; Mathieson, K.; Sher, A.

    2015-03-01

    Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. Subretinal photovoltaic arrays with 70μm pixels were used to convert pulsed near-IR light (880-915nm) into pulsed current to stimulate the nearby inner retinal neurons. Network-mediated responses of the retinal ganglion cells (RGCs) could be modulated by pulse width (1-20ms) and peak irradiance (0.5-10 mW/mm2). Similarly to normal vision, retinal response to prosthetic stimulation exhibited flicker fusion at high frequencies, adaptation to static images, and non-linear spatial summation. Spatial resolution was assessed in-vitro and in-vivo using alternating gratings with variable stripe width, projected with rapidly pulsed illumination (20-40Hz). In-vitro, average size of the electrical receptive fields in normal retina was 248+/-59μm - similar to their visible light RF size: 249+/-44μm. RGCs responded to grating stripes down to 67μm using photovoltaic stimulation in degenerate rat retina, and 28μm with visible light in normal retina. In-vivo, visual acuity in normally-sighted controls was 29+/-5μm/stripe, vs. 63+/-4μm/stripe in rats with subretinal photovoltaic arrays, corresponding to 20/250 acuity in human eye. With the enhanced acuity provided by eye movements and perceptual learning in human patients, visual acuity might exceed the 20/200 threshold of legal blindness. Ease of implantation and tiling of these wireless arrays to cover a large visual field, combined with their high resolution opens the door to highly functional restoration of sight.

  19. Imaging retinal ganglion cells: enabling experimental technology for clinical application.

    PubMed

    Smith, Corey A; Chauhan, Balwantray C

    2015-01-01

    Recent advances in clinical ophthalmic imaging have enhanced patient care. However, the ability to differentiate retinal neurons, such as retinal ganglion cells (RGCs), would advance many areas within ophthalmology, including the screening and monitoring of glaucoma and other optic neuropathies. Imaging at the single cell level would take diagnostics to the next level. Experimental methods have provided techniques and insight into imaging RGCs, however no method has yet to be translated to clinical application. This review provides an overview of the importance of non-invasive imaging of RGCs and the clinically relevant capabilities. In addition, we report on experimental data from wild-type mice that received an in vivo intravitreal injection of a neuronal tracer that labelled RGCs, which in turn were monitored for up to 100 days post-injection with confocal scanning laser ophthalmoscopy. We were able to demonstrate efficient and consistent RGC labelling with this delivery method and discuss the issue of cell specificity. This type of experimental work is important in progressing towards clinically applicable methods for monitoring loss of RGCs in glaucoma and other optic neuropathies. We discuss the challenges to translating these findings to clinical application and how this method of tracking RGCs in vivo could provide valuable structural and functional information to clinicians. PMID:25448921

  20. Enriched retinal ganglion cells derived from human embryonic stem cells.

    PubMed

    Gill, Katherine P; Hung, Sandy S C; Sharov, Alexei; Lo, Camden Y; Needham, Karina; Lidgerwood, Grace E; Jackson, Stacey; Crombie, Duncan E; Nayagam, Bryony A; Cook, Anthony L; Hewitt, Alex W; Pébay, Alice; Wong, Raymond C B

    2016-01-01

    Optic neuropathies are characterised by a loss of retinal ganglion cells (RGCs) that lead to vision impairment. Development of cell therapy requires a better understanding of the signals that direct stem cells into RGCs. Human embryonic stem cells (hESCs) represent an unlimited cellular source for generation of human RGCs in vitro. In this study, we present a 45-day protocol that utilises magnetic activated cell sorting to generate enriched population of RGCs via stepwise retinal differentiation using hESCs. We performed an extensive characterization of these stem cell-derived RGCs by examining the gene and protein expressions of a panel of neural/RGC markers. Furthermore, whole transcriptome analysis demonstrated similarity of the hESC-derived RGCs to human adult RGCs. The enriched hESC-RGCs possess long axons, functional electrophysiological profiles and axonal transport of mitochondria, suggestive of maturity. In summary, this RGC differentiation protocol can generate an enriched population of functional RGCs from hESCs, allowing future studies on disease modeling of optic neuropathies and development of cell therapies. PMID:27506453

  1. Melanopsin, photosensitive ganglion cells, and seasonal affective disorder.

    PubMed

    Roecklein, Kathryn A; Wong, Patricia M; Miller, Megan A; Donofry, Shannon D; Kamarck, Marissa L; Brainard, George C

    2013-03-01

    In two recent reports, melanopsin gene variations were associated with seasonal affective disorder (SAD), and in changes in the timing of sleep and activity in healthy individuals. New studies have deepened our understanding of the retinohypothalamic tract, which translates environmental light received by the retina into neural signals sent to a set of nonvisual nuclei in the brain that are responsible for functions other than sight including circadian, neuroendocrine and neurobehavioral regulation. Because this pathway mediates seasonal changes in physiology, behavior, and mood, individual variations in the pathway may explain why approximately 1-2% of the North American population develops mood disorders with a seasonal pattern (i.e., Major Depressive and Bipolar Disorders with a seasonal pattern, also known as seasonal affective disorder/SAD). Components of depression including mood changes, sleep patterns, appetite, and cognitive performance can be affected by the biological and behavioral responses to light. Specifically, variations in the gene sequence for the retinal photopigment, melanopsin, may be responsible for significant increased risk for mood disorders with a seasonal pattern, and may do so by leading to changes in activity and sleep timing in winter. The retinal sensitivity of SAD is hypothesized to be decreased compared to controls, and that further decrements in winter light levels may combine to trigger depression in winter. Here we outline steps for new research to address the possible role of melanopsin in seasonal affective disorder including chromatic pupillometry designed to measure the sensitivity of melanopsin containing retinal ganglion cells.

  2. Cytoarchitectonic study of the trigeminal ganglion in humans

    PubMed Central

    KRASTEV, DIMO STOYANOV; APOSTOLOV, ALEXANDER

    2013-01-01

    The trigeminal ganglion (TG), a cluster of pseudounipolar neurons, is located in the trigeminal impression of the temporal pyramid. It is covered by a sheath of the dura mater and arachnoid and is near the rear end of the cavernous sinus. The peripheral processes of the pseudounipolar cells are involved in the formation of the first and second branch and the sensory part of the third branch of the fifth cranial nerve, and the central ones form the sensory root of the nerve, which penetrates at the level of the middle cerebellar peduncle, aside from the pons, and terminate in the sensory nuclei of the trigeminal complex. We found that the primary sensory neurons involved in sensory innervation of the orofacial complex are a diverse group. Although they possess the general structure of pseudounipolar neurons, there are significant differences among them, seen in varying intensities of staining. Based on our investigations we classified the neurons into 7 groups, i.e. large, subdivided into light and dark, medium, also light and dark, and small light and dark, and, moreover, neurons with an irregular shape of their perikarya. Further research by applying various immunohistochemical methods will clarify whether differences in the morphological patterns of the neurons are associated with differences in the neurochemical composition of various neuronal types. PMID:26527926

  3. Enriched retinal ganglion cells derived from human embryonic stem cells

    PubMed Central

    Gill, Katherine P.; Hung, Sandy S. C.; Sharov, Alexei; Lo, Camden Y.; Needham, Karina; Lidgerwood, Grace E.; Jackson, Stacey; Crombie, Duncan E.; Nayagam, Bryony A.; Cook, Anthony L.; Hewitt, Alex W.; Pébay, Alice; Wong, Raymond C. B.

    2016-01-01

    Optic neuropathies are characterised by a loss of retinal ganglion cells (RGCs) that lead to vision impairment. Development of cell therapy requires a better understanding of the signals that direct stem cells into RGCs. Human embryonic stem cells (hESCs) represent an unlimited cellular source for generation of human RGCs in vitro. In this study, we present a 45-day protocol that utilises magnetic activated cell sorting to generate enriched population of RGCs via stepwise retinal differentiation using hESCs. We performed an extensive characterization of these stem cell-derived RGCs by examining the gene and protein expressions of a panel of neural/RGC markers. Furthermore, whole transcriptome analysis demonstrated similarity of the hESC-derived RGCs to human adult RGCs. The enriched hESC-RGCs possess long axons, functional electrophysiological profiles and axonal transport of mitochondria, suggestive of maturity. In summary, this RGC differentiation protocol can generate an enriched population of functional RGCs from hESCs, allowing future studies on disease modeling of optic neuropathies and development of cell therapies. PMID:27506453

  4. Developmental mechanisms that regulate retinal ganglion cell dendritic morphology

    PubMed Central

    Tian, Ning

    2011-01-01

    One of the fundamental features of retinal ganglion cells (RGCs) is that dendrites of individual RGCs are confined to one or a few narrow strata within the inner plexiform layer (IPL), and each RGC synapses only with a small group of presynaptic bipolar and amacrine cells with axons/dendrites ramified in the same strata to process distinct visual features. The underlying mechanisms which control the development of this laminar-restricted distribution pattern of RGC dendrites have been extensively studied, and it is still an open question whether the dendritic pattern of RGCs is determined by molecular cues or by activity-dependent refinement. Accumulating evidence suggests that both molecular cues and activity-dependent refinement might regulate RGC dendrites in a cell subtype-specific manner. However, identification of morphological subtypes of RGCs before they have achieved their mature dendritic pattern is a major challenge in the study of RGC dendritic development. This problem is now being circumvented through the use of molecular markers in genetically engineered mouse lines to identify RGC subsets early during development. Another unanswered fundamental question in the study of activity-dependent refinement of RGC dendrites is how changes in synaptic activity lead to the changes in dendritic morphology. Recent studies have started to shed light on the molecular basis of activity-dependent dendritic refinement of RGCs by showing that some molecular cascades control the cytoskeleton reorganization of RGCs. PMID:21542137

  5. Characteristics of sodium currents in rat geniculate ganglion neurons.

    PubMed

    Nakamura, Shiro; Bradley, Robert M

    2011-12-01

    Geniculate ganglion (GG) cell bodies of chorda tympani (CT), greater superficial petrosal (GSP), and posterior auricular (PA) nerves transmit orofacial sensory information to the rostral nucleus of the solitary tract. We have used whole cell recording to investigate the characteristics of the Na(+) channels in isolated Fluorogold-labeled GG neurons that innervate different peripheral receptive fields. GG neurons expressed two classes of Na(+) channels, TTX sensitive (TTX-S) and TTX resistant (TTX-R). The majority of GG neurons expressed TTX-R currents of different amplitudes. TTX-R currents were relatively small in 60% of the neurons but were large in 12% of the sampled population. In a further 28% of the neurons, TTX completely abolished all Na(+) currents. Application of TTX completely inhibited action potential generation in all CT and PA neurons but had little effect on the generation of action potentials in 40% of GSP neurons. Most CT, GSP, and PA neurons stained positively with IB(4), and 27% of the GSP neurons were capsaicin sensitive. The majority of IB(4)-positive GSP neurons with large TTX-R Na(+) currents responded to capsaicin, whereas IB(4)-positive GSP neurons with small TTX-R Na(+) currents were capsaicin insensitive. These data demonstrate the heterogeneity of GG neurons and indicate the existence of a subset of GSP neurons sensitive to capsaicin, usually associated with nociceptors. Since there are no reports of nociceptors in the GSP receptive field, the role of these capsaicin-sensitive neurons is not clear.

  6. Neurochemical properties of the middle cervical ganglion in the sheep.

    PubMed

    Arciszewski, Marcin Bartłomiej; Wasowicz, Krzysztof

    2006-01-01

    The neurochemical properties of the ovine middle cervical ganglion (MCG) were studied using antibodies raised against tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and galanin (GAL). Double-labelling immunocytochemistry revealed that the vast majority (95.5 +/- 0.8%) of postganglionic sympathetic MCG neurons expressed simultaneously both catecholamine-synthesizing enzymes (neurons were TH/DbetaH-positive). A large population of noradrenergic neurons exhibited immunoreactivity (IR) to NPY (62.2 +/- 2.2%), but single NPY-positive perikarya-lacking noradrenergic markers were also observed (2.0 +/- 0.3%). None of the examined MCG neuronal somata contained SP, CGRP, GAL or VIP. A moderate number of noradrenergic nerve fibres located amongst neuronal cell bodies was also found. In small number of these terminals the presence of NPYor GAL (but not CGRP or VIP) was detected. The ovine MCG was numerously innervated with SP-immunoreactive nerve fibres which sometimes formed basket-like formations around postganglionic neurons. The MCG exhibited a sparse CGRP-immunoreactive innervation and lacked VIP-positive nerve terminals. In many aspects the chemical coding of MCG postganglionic neurons and nerve terminals resembles that found in other mammalian cervico-thoracic paravertebral ganglia, but some important species-dependent differences exist. The functional implications of these differences remain to be elucidated. PMID:16447916

  7. The first described joint-associated intraneural ganglion cyst.

    PubMed

    Spinner, Robert J; Wang, Huan

    2011-12-01

    This article describes the identification of the first known specimen in which an articular origin for an intraneural cyst was recognized. Prompted by early citations in the 20th century of a valuable 1904 tibial intraneural ganglion housed at St. Bartholomew's Hospital in London, we traveled there to research it. We fortuitously discovered a citation to an earlier joint-related specimen, one that had not previously been referenced correctly in subsequent publications on intraneural cysts for more than a century. The original anatomic description dating to 1884, summarized in 3 lines in a museum catalog, was attributed to T. Swinford Edwards. This cadaveric specimen affected the deep branch of the ulnar nerve and arose from a carpal joint. Additional information was provided in a Transactions in 1884. An original drawing of the specimen was published in a textbook written in 1889 by Anthony Bowlby, a former curator, both of which credited F. (Frederick) Swinford Edwards, a demonstrator in anatomy and surgery at St. Bartholomew's. Unfortunately, the specimen could not be located and is presumed lost. To establish this specimen as the first known example of a joint-related intraneural cyst, we completed a review of >400 other cases and confirmed this statement. The first observation of an articular origin for an intraneural cyst, made by 2 eminent surgeons, has not been properly acknowledged. Considered with a modern perspective, this historical case solidifies the articular (synovial) origin for these unusual intraneural cysts, a finding that has important treatment implications.

  8. Enteric ganglionitis in rhesus macaques infected with simian immunodeficiency virus.

    PubMed

    Orandle, Marlene S; Veazey, Ronald S; Lackner, Andrew A

    2007-06-01

    Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection that can occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight into potential pathogenic mechanisms of GI disease. Ganglia from duodenum, ileum, and colon were examined in healthy and acutely infected macaques by using a combination of routine histology, double-label immunofluorescence and in situ hybridization. Evaluation of tissues from infected macaques showed progressive infiltration of myenteric ganglia by CD3+ T cells and IBA1+ macrophages beginning as early as 8 days postinfection. Quantitative image analysis revealed that the severity of myenteric ganglionitis increased with time after SIV infection and, in general, was more severe in ganglia from the small intestine than in ganglia from the colon. Despite an abundance of inflammatory cells in myenteric ganglia during acute infection, the ENS was not a target for virus infection. This study provides evidence that the ENS may be playing a role in the pathogenesis of GI disease and enteropathy in HIV-infected people.

  9. THE NISSL SUBSTANCE OF LIVING AND FIXED SPINAL GANGLION CELLS

    PubMed Central

    Deitch, Arline D.; Murray, Margaret R.

    1956-01-01

    Living chick embryo spinal ganglion neurons grown from 1 to 4 weeks in vitro were studied under the phase contrast microscope. In the peripheral cytoplasm of the earliest stages studied, a homogeneous, phase-dense material is seen which corresponds in location to the cytoplasmic basophil material of the same stages. As maturation proceeds, this material increases in extent, and becomes separated by lighter channels into discrete bodies. Short fixation by 1 per cent buffered osmium tetroxide followed by post-fixation with neutral buffered formalin does not significantly alter the size, shape, or distribution of any of the cytoplasmic components, and the fixed, hydrated cell is almost indistinguishable from the living cell. Dehydration causes some shrinkage of the fixed preparations, but if the photographs of the stained preparations are enlarged to correspond with those of the living cell, excellent correspondence can be made between at least the larger basophil masses and the larger dark masses seen with phase contrast. Fixation by a formalin-mercuric chloride procedure also results in satisfactory correspondence between the stained Nissl bodies and the phase-dark homogeneous areas. It is concluded that discrete Nissl bodies preexist in the living neuron and are essentially unchanged after good cytological fixation. Evidence is also presented of the presence of neurofibrils in the living state. PMID:13357508

  10. Shell nuclear explosions in degenerate dwarfs

    NASA Astrophysics Data System (ADS)

    Kuznetsov, O. A.; Tutukov, A. V.; Chechetkin, V. M.

    1989-08-01

    Numerical gas dynamics simulations are used to study shell nuclear explosions of degenerate carbon-oxygen dwarfs with masses of 1.17, 1.36, and 1.42 solar masses. It is assumed that the calorific capacity of the burning shell matter is between 5 X 10 to the 17th and 5 X 10 to the 18th erg/g. It is shown that, at a low calorific capacity, a remnant may form if the mass of the shell is less than 90 percent of the mass of the degenerate dwarf. In the case of high calorific capacity, a remnant may form only if the mass of the shell is less than half of the dwarf's mass.

  11. NEUTRINO PROCESSES IN PARTIALLY DEGENERATE NEUTRON MATTER

    SciTech Connect

    Bacca, S.; Hally, K.; Liebendoerfer, M.; Perego, A.; Pethick, C. J.; Schwenk, A.

    2012-10-10

    We investigate neutrino processes for conditions reached in simulations of core-collapse supernovae. In regions where neutrino-matter interactions play an important role, matter is partially degenerate, and we extend earlier work that addressed the degenerate regime. We derive expressions for the spin structure factor in neutron matter, which is a key quantity required for evaluating rates of neutrino processes. We show that, for essentially all conditions encountered in the post-bounce phase of core-collapse supernovae, it is a very good approximation to calculate the spin relaxation rates in the nondegenerate limit. We calculate spin relaxation rates based on chiral effective field theory interactions and find that they are typically a factor of two smaller than those obtained using the standard one-pion-exchange interaction alone.

  12. Inflammation in age-related macular degeneration.

    PubMed

    Ozaki, Ema; Campbell, Matthew; Kiang, Anna-Sophia; Humphries, Marian; Doyle, Sarah L; Humphries, Peter

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly individuals in the developed world, affecting 30-50 million people worldwide. AMD primarily affects the macular region of the retina that is responsible for the majority of central, color and daytime vision. The presence of drusen, extracellular protein aggregates that accumulate under the retinal pigment epithelium (RPE), is a major pathological hallmark in the early stages of the disease. The end stage 'dry' and 'wet' forms of the disease culminate in vision loss and are characterized by focal degeneration of the RPE and cone photoreceptors, and choroidal neovascularization (CNV), respectively. Being a multifactorial and genetically heterogeneous disease, the pathophysiology of AMD remains unclear, yet, there is ample evidence supporting immunological and inflammatory processes. Here, we review the recent literature implicating some of these immune processes in human AMD and in animal models. PMID:24664703

  13. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  14. Immunology of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

  15. Dichromatic Langmuir waves in degenerate quantum plasma

    SciTech Connect

    Dubinov, A. E. Kitayev, I. N.

    2015-06-15

    Langmuir waves in fully degenerate quantum plasma are considered. It is shown that, in the linear approximation, Langmuir waves are always dichromatic. The low-frequency component of the waves corresponds to classical Langmuir waves, while the high-frequency component, to free-electron quantum oscillations. The nonlinear problem on the profile of dichromatic Langmuir waves is solved. Solutions in the form of a superposition of waves and in the form of beatings of its components are obtained.

  16. Degenerate Bose gases with uniform loss

    NASA Astrophysics Data System (ADS)

    Grišins, Pjotrs; Rauer, Bernhard; Langen, Tim; Schmiedmayer, Jörg; Mazets, Igor E.

    2016-03-01

    We theoretically investigate a weakly interacting degenerate Bose gas coupled to an empty Markovian bath. We show that in the universal phononic limit the system evolves towards an asymptotic state where an emergent temperature is set by the quantum noise of the outcoupling process. For situations typically encountered in experiments, this mechanism leads to significant cooling. Such dissipative cooling supplements conventional evaporative cooling and dominates in settings where thermalization is highly suppressed, such as in a one-dimensional quasicondensate.

  17. [Epidemiology of age related macular degeneration].

    PubMed

    Leveziel, N; Delcourt, C; Zerbib, J; Dollfus, H; Kaplan, J; Benlian, P; Coscas, G; Souied, E H; Soubrane, G

    2009-06-01

    Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease. PMID:19515460

  18. Sarcomatous degeneration in a nasopharyngeal angiofibroma.

    PubMed

    Donald, P J

    1979-01-01

    Malignant degeneration in a juvenile nasopharyngeal angiofibroma has been reported in the literature in only four patients. All of these persons had been previously treated for cure with gamma irradiation. The case report of a 47-year-old man with a 31-year history of nasal obstruction is presented. A recurrence excised 18 months after initial removal of an angiofibroma revealed the surprising diagnosis of fibrosarcoma.

  19. Calabi-Yau manifolds and their degenerations.

    PubMed

    Tosatti, Valentino

    2012-07-01

    Calabi-Yau manifolds are geometric objects of central importance in several branches of mathematics, including differential geometry, algebraic geometry, and mathematical physics. In this paper, we give a brief introduction to the subject aimed at a general mathematical audience and present some of our results that shed some light on the possible ways in which families of Calabi-Yau manifolds can degenerate. PMID:22257362

  20. Recombination-generation currents in degenerate semiconductors

    NASA Technical Reports Server (NTRS)

    Von Roos, O.

    1978-01-01

    The classical Shockley-Read-Hall theory of free carrier recombination and generation via traps is extended to degenerate semiconductors. A concise and simple expression is found which avoids completely the concept of a Fermi level, a concept which is alien to nonequilibrium situations. Assumptions made in deriving the recombination generation current are carefully delineated and are found to be basically identical to those made in the original theory applicable to nondegenerate semiconductors.

  1. Propagation of disturbances in degenerate quantum systems

    NASA Astrophysics Data System (ADS)

    Chancellor, Nicholas; Haas, Stephan

    2011-07-01

    Disturbances in gapless quantum many-body models are known to travel an unlimited distance throughout the system. Here, we explore this phenomenon in finite clusters with degenerate ground states. The specific model studied here is the one-dimensional J1-J2 Heisenberg Hamiltonian at and close to the Majumdar-Ghosh point. Both open and periodic boundary conditions are considered. Quenches are performed using a local magnetic field. The degenerate Majumdar-Ghosh ground state allows disturbances which carry quantum entanglement to propagate throughout the system and thus dephase the entire system within the degenerate subspace. These disturbances can also carry polarization, but not energy, as all energy is stored locally. The local evolution of the part of the system where energy is stored drives the rest of the system through long-range entanglement. We also examine approximations for the ground state of this Hamiltonian in the strong field limit and study how couplings away from the Majumdar-Ghosh point affect the propagation of disturbances. We find that even in the case of approximate degeneracy, a disturbance can be propagated throughout a finite system.

  2. Hypertrophic olivary degeneration secondary to pontine haemorrhage.

    PubMed

    Wein, Sara; Yan, Bernard; Gaillard, Frank

    2015-07-01

    We report a 58-year-old man who developed hyptertrophic olivary degeneration (HOD) after haemorrhage of a cavernous malformation in the pons. Lesions of the triangle of Guillain and Mollaret (the dentatorubro-olivary pathway) may lead to HOD, a secondary transsynaptic degeneration of the inferior olivary nucleus. HOD is considered unique because the degenerating olive initially becomes hypertrophic rather than atrophic. The primary lesion causing pathway interruption is often haemorrhage, either due to hypertension, trauma, surgery or, as in our patient, a vascular malformation such as a cavernoma. Ischaemia and demyelination can also occasionally be the inciting events. The classic clinical presentation of HOD is palatal myoclonus, although not all patients with HOD develop this symptom. The imaging features of HOD evolve through characteristic phases. The clue to the diagnosis of HOD is recognition of the distinct imaging stages and identification of a remote primary lesion in the triangle of Guillain and Mollaret. Familiarity with the classic imaging findings of this rare phenomenon is necessary in order to avoid misdiagnosis and prevent unnecessary intervention.

  3. Molecular mechanisms in the initiation phase of Wallerian degeneration.

    PubMed

    Chang, Biao; Quan, Qi; Lu, Shibi; Wang, Yu; Peng, Jiang

    2016-08-01

    Axonal degeneration is an early hallmark of nerve injury and many neurodegenerative diseases. The discovery of the Wallerian degeneration slow mutant mouse, in which axonal degeneration is delayed, revealed that Wallerian degeneration is an active progress and thereby illuminated the mechanisms underlying axonal degeneration. Nicotinamide mononucleotide adenylyltransferase 2 and sterile alpha and armadillo motif-containing protein 1 play essential roles in the maintenance of axon integrity by regulating the level of nicotinamide adenine dinucleotide, which seems to be the key molecule involved in the maintenance of axonal health. However, the function of nicotinamide mononucleotide remains debatable, and we discuss two apparently conflicting roles of nicotinamide mononucleotide in Wallerian degeneration. In this article, we focus on the roles of these molecules in the initiation phase of Wallerian degeneration to improve our understanding of the mechanisms underpinning this phenomenon. PMID:27062141

  4. Bistratified ganglion cells of rabbit retina: neural architecture for contrast-independent visual responses.

    PubMed

    Famiglietti, Edward V

    2009-01-01

    Bistratified (BS) ganglion cells have long been recognized in vertebrate retina. Thirty years ago, it became clear that bistratification allows the integration of ON and OFF retinal pathways to produce contrast-independent responses in ganglion cells. Best studied is the type 1 bistratified (BS1) ganglion cell of rabbit retina, the physiologically well-characterized ON-OFF directionally selective (DS) ganglion cell, which is co-stratified with the two types of starburst amacrine (SA) cells in sublaminae a and b of the inner plexiform layer (IPL). DS responses have recently been documented in the latter. In this report, BS1 cells are further studied and are used as "fiducials" to characterize a second type of BS ganglion cell. An example of a possible third type is shown to be distinct from examples of BS1 and BS2 cells. All three have two distinct, narrowly stratified arborizations, one in sublamina a and one in sublamina b. All have similar dimensions, except for their dendritic trees, differing also in branching pattern. BS1 cells have compact, regular, highly branched trees; BS2 cells have significantly larger, more sparsely branched, irregular, radiate trees; the proposed BS3 type is intermediate in field size, and its branching pattern is different from the first two. BS2 and BS3 cells are co-stratified, branching nearer to the margins of the IPL, out of range of SA cells. In a previous report by others, illustrating the morphology of intracellularly stained ganglion cells, one example each of both "orientation-selective" ganglion cells and "uniformity detectors" resembles the BS2 cell. A rationale is presented for correlating BS2 cells with uniformity detectors.

  5. Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

    NASA Technical Reports Server (NTRS)

    Morin, Lawrence P.; Blanchard, Jane H.; Provencio, Ignacio

    2003-01-01

    The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

  6. [New drug therapy for retinal degeneration].

    PubMed

    Ohguro, Hiroshi

    2008-01-01

    Retinitis pigmentosa (RP) is an inherited retinal degeneration characterized by nyctalopia, ring scotoma, and bone-spicule pigmentation of the retina. So far, no effective therapy has been found for RP. As a possible molecular etiology of RP, retina-specific gene deficits are most likely involved, but little has been identified in terms of intracellular mechanisms leading to retinal photoreceptor cell death at post-translational levels. In order to find an effective therapy for RP, we must look for underlying common mechanisms that are responsible for the development of RP, instead of designing a specific therapy for each of the RP types with different causes. Therefore, in the present study, several animal models with different causes of RP were studied, including (1)Royal College of Surgeons (RCS) rats with a deficit of retinal pigment epithelium (RPE) function caused by rhodopsin mutation; (2) P23H rats, (3) S334ter rats, (4) photo stress rats, (5) retinal degeneration (rd) mice with a deficit of phosphodiesterase(PDE) function; and (6) cancer-associated retinopathy (CAR) model rats with a deficit of recoverin-dependent photoreceptor adaptation function. In each of these models, the following assessments were made in order to elucidate common pathological mechanisms among the models: (1) retinal function assessed by electroretinogram (ERG), (2) retinal morphology, (3) retinoid analysis, (4) rhodopsin regeneration, (5) rhodopsin phosphorylation and dephosphorylation, and (6) cytosolic cGMP levels. We found that unregulated photoreceptor adaptation processes caused by an imbalance of rhodopsin phosphorylation and dephosphorylation caused retinal dysfunction leading to photoreceptor cell death. As possible candidate drugs for normalizing these retinal dysfunctions and stopping further retinal degeneration, nilvadipine, a Ca channel blocker, retinoid derivatives, and anthocyanine were chosen and tested to determine their effect on the above animal models with

  7. Synaptic remodeling generates synchronous oscillations in the degenerated outer mouse retina

    PubMed Central

    Haq, Wadood; Arango-Gonzalez, Blanca; Zrenner, Eberhart; Euler, Thomas; Schubert, Timm

    2014-01-01

    During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with remnant cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs), we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from interneurons such as HCs and/or possibly interplexiform cells. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type) cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates) the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells. PMID:25249942

  8. Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration

    PubMed Central

    Kimura, Atsuko; Namekata, Kazuhiko; Guo, Xiaoli; Harada, Chikako; Harada, Takayuki

    2016-01-01

    Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP), and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs). Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration. PMID:27657046

  9. Gain-of-function nature of Cav1.4 L-type calcium channels alters firing properties of mouse retinal ganglion cells

    PubMed Central

    Knoflach, Dagmar; Schicker, Klaus; Glösmann, Martin; Koschak, Alexandra

    2015-01-01

    Proper function of Cav1.4 L-type calcium channels is crucial for neurotransmitter release in the retina. Our understanding about how different levels of Cav1.4 channel activity affect retinal function is still limited. In the gain-of-function mouse model Cav1.4-IT we expected a reduction in the photoreceptor dynamic range but still transmission toward retinal ganglion cells. A fraction of Cav1.4-IT ganglion cells responded to light stimulation in multielectrode array recordings from whole-mounted retinas, but showed a significantly delayed response onset. Another significant number of cells showed higher activity in darkness. In addition to structural remodeling observed at the first retinal synapse of Cav1.4-IT mice the functional data suggested a loss of contrast enhancement, a fundamental feature of our visual system. In fact, Cav1.4-IT mouse retinas showed a decline in spatial response and changes in their contrast sensitivity profile. Photoreceptor degeneration was obvious from the nodular structure of cone axons and enlarged pedicles which partly moved toward the outer nuclear layer. Loss of photoreceptors was also expressed as reduced expression of proteins involved in chemical and electrical transmission, as such metabotropic glutamate receptor mGluR6 and the gap junction protein Connexin 36. Such gross changes in retinal structure and function could also explain the diminished visual performance of CSNB2 patients. The expression pattern of the plasma-membrane calcium ATPase 1 which participates in the maintenance of the intracellular calcium homeostasis in photoreceptors was changed in Cav1.4-IT mice. This might be part of a protection mechanism against increased calcium influx, as this is suggested for Cav1.4-IT channels. PMID:26274509

  10. Protection of Retinal Ganglion Cells and Retinal Vasculature by Lycium Barbarum Polysaccharides in a Mouse Model of Acute Ocular Hypertension

    PubMed Central

    Mi, Xue-Song; Feng, Qian; Lo, Amy Cheuk Yin; Chang, Raymond Chuen-Chung; Lin, Bin; Chung, Sookja Kim; So, Kwok-Fai

    2012-01-01

    Acute ocular hypertension (AOH) is a condition found in acute glaucoma. The purpose of this study is to investigate the protective effect of Lycium barbarum polysaccharides (LBP) and its protective mechanisms in the AOH insult. LBP has been shown to exhibit neuroprotective effect in the chronic ocular hypertension (COH) experiments. AOH mouse model was induced in unilateral eye for one hour by introducing 90 mmHg ocular pressure. The animal was fed with LBP solution (1 mg/kg) or vehicle daily from 7 days before the AOH insult till sacrifice at either day 4 or day 7 post insult. The neuroprotective effects of LBP on retinal ganglion cells (RGCs) and blood-retinal-barrier (BRB) were evaluated. In control AOH retina, loss of RGCs, thinning of IRL thickness, increased IgG leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of IRL thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein and the recovery of the blood vessel density when compared with vehicle-treated AOH retina. Moreover, we found that LBP provides neuroprotection by down-regulating RAGE, ET-1, Aβ and AGE in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. The present study suggests that LBP could prevent damage to RGCs from AOH-induced ischemic injury; furthermore, through its effects on blood vessel protection, LBP would also be a potential treatment for vascular-related retinopathy. PMID:23094016

  11. DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma.

    PubMed

    Kim, K-Y; Perkins, G A; Shim, M S; Bushong, E; Alcasid, N; Ju, S; Ellisman, M H; Weinreb, R N; Ju, W-K

    2015-01-01

    Glaucoma is the leading cause of irreversible blindness and is characterized by slow and progressive degeneration of the optic nerve head axons and retinal ganglion cell (RGC), leading to loss of visual function. Although oxidative stress and/or alteration of mitochondrial (mt) dynamics induced by elevated intraocular pressure (IOP) are associated with this neurodegenerative disease, the mechanisms that regulate mt dysfunction-mediated glaucomatous neurodegeneration are poorly understood. Using a mouse model of glaucoma, DBA/2J (D2), which spontaneously develops elevated IOP, as well as an in vitro RGC culture system, we show here that oxidative stress, as evidenced by increasing superoxide dismutase 2 (SOD2) and mt transcription factor A (Tfam) protein expression, triggers mt fission and loss by increasing dynamin-related protein 1 (DRP1) in the retina of glaucomatous D2 mice as well as in cultured RGCs exposed to elevated hydrostatic pressure in vitro. DRP1 inhibition by overexpressing DRP1 K38A mutant blocks mt fission and triggers a subsequent reduction of oxidative stress, as evidenced by decreasing SOD2 and Tfam protein expression. DRP1 inhibition promotes RGC survival by increasing phosphorylation of Bad at serine 112 in the retina and preserves RGC axons by maintaining mt integrity in the glial lamina of glaucomatous D2 mice. These findings demonstrate an important vicious cycle involved in glaucomatous neurodegeneration that starts with elevated IOP producing oxidative stress; the oxidative stress then leads to mt fission and a specific form of mt dysfunction that generates further oxidative stress, thus perpetuating the cycle. Our findings suggest that DRP1 is a potential therapeutic target for ameliorating oxidative stress-mediated mt fission and dysfunction in RGC and its axons during glaucomatous neurodegeneration. Thus, DRP1 inhibition may provide a new therapeutic strategy for protecting both RGCs and their axons in glaucoma and other optic

  12. Spatially restricted electrical activation of retinal ganglion cells in the rabbit retina by hexapolar electrode return configuration

    NASA Astrophysics Data System (ADS)

    Habib, Amgad G.; Cameron, Morven A.; Suaning, Gregg J.; Lovell, Nigel H.; Morley, John W.

    2013-06-01

    Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed ‘phosphenes’. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

  13. Tetrandrine protects mouse retinal ganglion cells from ischemic injury

    PubMed Central

    Li, Weiyi; Yang, Chen; Lu, Jing; Huang, Ping; Barnstable, Colin J; Zhang, Chun; Zhang, Samuel S

    2014-01-01

    This study aimed to determine the protective effects of tetrandrine (Tet) on murine ischemia-injured retinal ganglion cells (RGCs). For this, we used serum deprivation cell model, glutamate and hydrogen peroxide (H2O2)-induced RGC-5 cell death models, and staurosporine-differentiated neuron-like RGC-5 in vitro. We also investigated cell survival of purified primary-cultured RGCs treated with Tet. An in vivo retinal ischemia/reperfusion model was used to examine RGC survival after Tet administration 1 day before ischemia. We found that Tet affected RGC-5 survival in a dose- and time-dependent manner. Compared to dimethyl sulfoxide treatment, Tet increased the numbers of RGC-5 cells by 30% at 72 hours. After 48 hours, Tet protected staurosporine-induced RGC-5 cells from serum deprivation-induced cell death and significantly increased the relative number of cells cultured with 1 mM H2O2 (P<0.01). Several concentrations of Tet significantly prevented 25-mM-glutamate-induced cell death in a dose-dependent manner. Tet also increased primary RGC survival after 72 and 96 hours. Tet administration (10 μM, 2 μL) 1 day before retinal ischemia showed RGC layer loss (greater survival), which was less than those in groups with phosphate-buffered saline intravitreal injection plus ischemia in the central (P=0.005, n=6), middle (P=0.018, n=6), and peripheral (P=0.017, n=6) parts of the retina. Thus, Tet conferred protective effects on serum deprivation models of staurosporine-differentiated neuron-like RGC-5 cells and primary cultured murine RGCs. Furthermore, Tet showed greater in vivo protective effects on RGCs 1 day after ischemia. Tet and ciliary neurotrophic factor maintained the mitochondrial transmembrane potential (ΔΨm) of primary cultured RGCs and inhibited the expression of activated caspase-3 and bcl-2 in ischemia/reperfusion-insult retinas. PMID:24711693

  14. Sluggish and Brisk Ganglion Cells Detect Contrast With Similar Sensitivity

    PubMed Central

    Xu, Ying; Dhingra, Narender K.; Smith, Robert G.; Sterling, Peter

    2010-01-01

    Roughly half of all ganglion cells in mammalian retina belong to the broad class, termed “sluggish.” Many of these cells have small receptive fields and project via lateral geniculate nuclei to visual cortex. However, their possible contributions to perception have been largely ignored because sluggish cells seem to respond weakly compared with the more easily studied “brisk” cells. By selecting small somas under infrared DIC optics and recording with a loose seal, we could routinely isolate sluggish cells. When a spot was matched spatially and temporally to the receptive field center, most sluggish cells could detect the same low contrasts as brisk cells. Detection thresholds for the two groups determined by an “ideal observer” were similar: threshold contrast for sluggish cells was 4.7 ± 0.5% (mean ± SE), and for brisk cells was 3.4 ± 0.3% (Mann-Whitney test: P > 0.05). Signal-to-noise ratios for the two classes were also similar at low contrast. However, sluggish cells saturated at somewhat lower contrasts (contrast for half-maximum response was 14 ± 1 vs. 19 ± 2% for brisk cells) and were less sensitive to higher temporal frequencies (when the stimulus frequency was increased from 2 to 4 Hz, the response rate fell by 1.6-fold). Thus the sluggish cells covered a narrower dynamic range and a narrower temporal bandwidth, consistent with their reported lower information rates. Because information per spike is greater at lower firing rates, sluggish cells may represent “cheaper” channels that convey less urgent visual information at a lower energy cost. PMID:15601731

  15. Melatonin modulates M4-type ganglion-cell photoreceptors.

    PubMed

    Pack, W; Hill, D D; Wong, K Y

    2015-09-10

    In the retina, melatonin is secreted at night by rod/cone photoreceptors and serves as a dark-adaptive signal. Melatonin receptors have been found in many retinal neurons including melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting it could modulate the physiology of these inner retinal photoreceptors. Here, we investigated whether melatonin modulates the alpha-like M4-type ipRGCs, which are believed to mediate image-forming vision as well as non-image-forming photoresponses. Applying melatonin during daytime (when endogenous melatonin secretion is low) caused whole-cell-recorded M4 cells' rod/cone-driven depolarizing photoresponses to become broader and larger, whereas the associated elevation in spike rate was reduced. Melanopsin-based light responses were not affected significantly. Nighttime application of the melatonin receptor antagonist luzindole also altered M4 cells' rod/cone-driven light responses but in the opposite ways: the duration and amplitude of the graded depolarization were reduced, whereas the accompanying spiking increase was enhanced. These luzindole-induced changes confirmed that M4 cells are modulated by endogenous melatonin. Melatonin could induce the above effects by acting directly on M4 cells because immunohistochemistry detected MT1 receptors in these cells, although it could also act presynaptically. Interestingly, the daytime and nighttime recordings showed significant differences in resting membrane potential, spontaneous spike rate and rod/cone-driven light responses, suggesting that M4 cells are under circadian control. This is the first report of a circadian variation in ipRGCs' resting properties and synaptic input, and of melatoninergic modulation of ipRGCs. PMID:26141846

  16. Sphenopalatine ganglion stimulation for the treatment of cluster headache

    PubMed Central

    Puche, Miguel; Garcia, Ana; Gascón, Francisco

    2014-01-01

    Cluster headache is a severe, debilitating disorder with pain that ranks among the most severe known to humans. Patients with cluster headaches have few therapeutic options and further, 10–20% develop drug-resistant attacks. The often brief duration of cluster attacks makes abortive therapy a challenge, and preventive medications are almost always provided to patients, but the side effects of these preventive medications can be significant. The sphenopalatine ganglion (SPG) is believed to play a role in headache pain and cranial autonomic symptoms associated with cluster headache, which is a result of activation of the trigeminal-autonomic reflex. For over 100 years, the SPG has been a clinical target to treat primary headache disorders using pharmacologic and nonpharmacologic methods. Radiofrequency lesioning and nerve-resection therapies, while initially beneficial, are irreversible procedures, and the use of neurostimulation provides one method of interfacing with the neural pathways without causing permanent damage to neural tissue. SPG neurostimulation is both reversible and adjustable, and has recently been tested in both proof-of-concept work and in a randomized, sham-controlled trial for the treatment of cluster headache. A randomized, sham-controlled study of 32 patients was performed to evaluate further the use of SPG stimulation for the acute treatment of chronic cluster headache. Of the 32 patients, 28 completed the randomized experimental period. Overall, 68% of patients experienced an acute response, a frequency response, or both. In this study the majority of adverse events were related to the implantation procedure, which typically resolved or remained mild in nature at 3 months following the implant procedure. This and other studies highlight the promise of using SPG stimulation to treat the pain-associated cluster headache. SPG stimulation could be a safe and effective option for chronic cluster headache. PMID:24790646

  17. Spiral ganglion outgrowth and hearing development in p75-deficient mice.

    PubMed

    Brors, Dominik; Hansen, Stefan; Mlynski, Robert; Volkenstein, Stefan; Aletsee, Christoph; Sendtner, Michael; Ryan, Allen F; Dazert, Stefan

    2008-01-01

    To explore the role of nerve growth factor receptor p75(NTR) during the terminal neuronal development of the mammalian cochlea the onset of hearing and the in vitro response of spiral ganglion neurites to neurotrophin 3 (NT-3), which is known to play a critical role during neonatal inner ear development, were investigated in p75(NTR)-deficient mice (p75(NTR)-/-). Auditory-evoked brain stem response recordings from p75(NTR)-/- and wild-type (WT) littermates were measured from postnatal days (PD) 8 to 23. Additionally, spiral ganglion explants from p75(NTR)-/- and WT animals were dissected and cultured in an organotypic tissue culture system. In both groups, spiral ganglion neurite outgrowth was analyzed with and without NT-3 supplementation. No significant differences in the onset of hearing of mutant mice compared to the WT mice were detected, and both groups showed a similar development of hearing until PD 23. After stimulation with NT-3, neurite outgrowth was enhanced in both p75(NTR)-/- and WT mice. However, neurites from p75(NTR)-/- spiral ganglion explants were longer in both culture conditions. Moreover, NT-3 did not significantly enhance neurite number in p75(NTR)-/-, as it did in WT mice. P75(NTR) has a remarkable influence on spiral ganglion neurite growth behavior. However, p75(NTR) does not seem to be essential for the development of basic hearing function in the first 3 postnatal weeks.

  18. Spiral ganglion outgrowth and hearing development in p75-deficient mice.

    PubMed

    Brors, Dominik; Hansen, Stefan; Mlynski, Robert; Volkenstein, Stefan; Aletsee, Christoph; Sendtner, Michael; Ryan, Allen F; Dazert, Stefan

    2008-01-01

    To explore the role of nerve growth factor receptor p75(NTR) during the terminal neuronal development of the mammalian cochlea the onset of hearing and the in vitro response of spiral ganglion neurites to neurotrophin 3 (NT-3), which is known to play a critical role during neonatal inner ear development, were investigated in p75(NTR)-deficient mice (p75(NTR)-/-). Auditory-evoked brain stem response recordings from p75(NTR)-/- and wild-type (WT) littermates were measured from postnatal days (PD) 8 to 23. Additionally, spiral ganglion explants from p75(NTR)-/- and WT animals were dissected and cultured in an organotypic tissue culture system. In both groups, spiral ganglion neurite outgrowth was analyzed with and without NT-3 supplementation. No significant differences in the onset of hearing of mutant mice compared to the WT mice were detected, and both groups showed a similar development of hearing until PD 23. After stimulation with NT-3, neurite outgrowth was enhanced in both p75(NTR)-/- and WT mice. However, neurites from p75(NTR)-/- spiral ganglion explants were longer in both culture conditions. Moreover, NT-3 did not significantly enhance neurite number in p75(NTR)-/-, as it did in WT mice. P75(NTR) has a remarkable influence on spiral ganglion neurite growth behavior. However, p75(NTR) does not seem to be essential for the development of basic hearing function in the first 3 postnatal weeks. PMID:18663291

  19. Multiple innervation of normal and re-innervated parasympathetic neurones in the frog cardiac ganglion.

    PubMed Central

    Dennis, M J; Sargent, P B

    1978-01-01

    1. Multiple innervation of parasympathetic neurones was examined in normal and re-innervated frog cardiac ganglia. The number of synaptic inputs impinging upon individual ganglion cells was determined by recording intracellularly and stimulating the vagosympathetic nerves. 2. In unoperated cardiac ganglia most neurones (93%) received a large, suprathreshold synaptic input. Some ganglion cells received additional, small synaptic inputs. Roughly equal numbers of cells encountered were singly and doubly innervated, and only 8% received more than two inputs. 3. Re-innervation of cardiac ganglion cells began three weeks after bilateral crush of the vagosympathetic nerves. By 7 weeks more than 90% of the ganglion cells were re-innervated. At this stage the pattern of multiple innervation was significantly different than normal: doubly innervated neurones outnumbered singly innervated ones, and 31% of the cells encountered received more than two inputs. This pattern was stable for at least a year. 4. These results indicate that polyneuronal innervation of cardiac ganglion cells is more widespread after re-innervation than it is normally and, furthermore, that synapse elimination does not occur during re-innervation of these cells. Images Plate 1 PMID:212557

  20. Mosaic properties of midget and parasol ganglion cells in the marmoset retina.

    PubMed

    Szmajda, Brett A; Grünert, Ulrike; Martin, Paul R

    2005-01-01

    We measured mosaic properties of midget and parasol ganglion cells in the retina of a New World monkey, the common marmoset Callithrix jacchus . We addressed the functional specialization of these populations for color and spatial vision, by comparing the mosaic of ganglion cells in dichromatic ("red-green color blind") and trichromatic marmosets. Ganglion cells were labelled by photolytic amplification of retrograde marker ("photofilling") following injections into the lateral geniculate nucleus, or by intracellular injection in an in vitro retinal preparation. The dendritic-field size, shape, and overlap of neighboring cells were measured. We show that in marmosets, both midget and parasol cells exhibit a radial bias, so that the long axis of the dendritic field points towards the fovea. The radial bias is similar for parasol cells and midget cells, despite the fact that midget cell dendritic fields are more elongated than are those of parasol cells. The dendritic fields of midget ganglion cells from the same (ON or OFF) response-type array show very little overlap, consistent with the low coverage of the midget mosaic in humans. No large differences in radial bias, or overlap, were seen on comparing retinae from dichromatic and trichromatic animals. These data suggest that radial bias in ganglion cell populations is a consistent feature of the primate retina. Furthermore, they suggest that the mosaic properties of the midget cell population are associated with high spatial resolution rather than being specifically associated with trichromatic color vision. PMID:16212698

  1. Retinal Ganglion Cell Topography and Retinal Resolution in the Baikal Seal (Pusa sibirica).

    PubMed

    Mass, Alla M; Supin, Alexander Y

    2016-01-01

    The total number, size, topographic distribution, and cell density of ganglion cells were studied in retinal wholemounts of Baikal seals (Pusa sibirica). The ganglion cell size varied from 10 to 38 μm. A distinct cell group consisted of large ganglion cells of more than 30 μm in diameter. The topographic distribution of ganglion cells showed a definite area of high cell density similar to the area centralis of terrestrial carnivores. This area was located approximately 6-7 mm dorsotemporally of the geometric center of the wholemount. In this area, the peak cell densities in two wholemounts were 3,800 and 3,400 cells/mm2 (mean 3,600 cells/mm2). With a posterior nodal distance of 24 mm (underwater), this density corresponds to 631 cells/square degree. These values predict a retinal resolution of 2.4' in water and 3.0' in air. The topographic distribution of large cells featured the highest density in the same location as the total ganglion cell population. PMID:27529170

  2. Vector polarons in a degenerate electron system

    NASA Astrophysics Data System (ADS)

    Clougherty, Dennis P.; Foell, Charles A.

    2004-08-01

    We consider a one-dimensional model of an electron in a doubly (or nearly) degenerate band that interacts with elastic distortions. We show that the electron equations of motion reduce to a set of coupled nonlinear Schrödinger equations. For the case of interband electron-phonon coupling stemming from local Jahn-Teller interactions, multicomponent self-localized polaron solutions-vector polarons- are described and classified. The phase diagram for the different types of vector polarons in this model is presented. By interpreting the components of the orbital doublet as those of spin- (1)/(2) , our results can also be used to describe bound magnetic polarons.

  3. Relativistic Bernstein waves in a degenerate plasma

    SciTech Connect

    Ali, Muddasir; Hussain, Azhar; Murtaza, G.

    2011-09-15

    Bernstein mode for a relativistic degenerate electron plasma is investigated. Using relativistic Vlasov-Maxwell equations, a general expression for the conductivity tensor is derived and then employing Fermi-Dirac distribution function a generalized dispersion relation for the Bernstein mode is obtained. Two limiting cases, i.e., non-relativistic and ultra-relativistic are discussed. The dispersion relations obtained are also graphically presented for some specific values of the parameters depicting how the propagation characteristics of Bernstein waves as well as the Upper Hybrid oscillations are modified with the increase in plasma number density.

  4. Aneutronic Fusion in a Degenerate Plasma

    SciTech Connect

    S. Son; N.J. Fisch

    2004-09-03

    In a Fermi-degenerate plasma, the electronic stopping of a slow ion is smaller than that given by the classical formula, because some transitions between the electron states are forbidden. The bremsstrahlung losses are then smaller, so that the nuclear burning of an aneutronic fuel is more efficient. Consequently, there occurs a parameter regime in which self-burning is possible. Practical obstacles in this regime that must be overcome before net energy can be realized include the compression of the fuel to an ultra dense state and the creation of a hot spot.

  5. Neuropeptides, amines and amino acids in an elementary insect ganglion: functional and chemical anatomy of the unfused abdominal ganglion.

    PubMed

    Nässel, D R

    1996-01-01

    The insect ventral nerve cord consists of metamerically repeated ganglia subserving the thoracic and abdominal segments. The abdominal ganglia control basic functions such as respiration, circulation, heartbeat, diuresis, hindgut motility, functions of the genitalia and ovipositor and abdominal posture. Some of this control is by efferent innervation of target tissues but hormonal control also is exerted by abdominal neurosecretory cells via release from neurohemal organs or other release sites. The present review summarizes what is known about the distribution of neurotransmitters, monoamines and neuropeptides in the abdominal ganglia of different insect species. Special emphasis is on the unfused abdominal ganglion, since this is the least complex of all central ganglia and therefore may reveal the minimum number of neuroactive compounds utilized in neurotransmission, neuromodulation and neurohormonal control. Both GABA and glutamate are present in both interneurons and motoneurons, whereas biogenic amines such as serotonin, dopamine and histamine are found primarily in interneurons (although some cases of sensory cells and efferent neurons are known). Octopamine can be seen both in interneurons, efferent neurons and neurosecretory cells. A large number (about 20 different main types) of neuropeptides has been indicated in abdominal ganglia. Each peptide has a very specific distribution pattern. Depending on the peptide type, the localization is known to be in interneurons, neurosecretory cells or motoneurons, or combinations of these. The structure and known functions of the different neuropeptides in different insect species are summarized in some detail. Both GABA and glutamate appear to have roles as fast neurotransmitters, whereas amines and neuropeptides seem to have modulatory roles both within the CNS and at peripheral targets. After a comprehensive overview of different substances in studied insect species, the unfused abdominal ganglia from the moth

  6. [Histoenzymologic features of adrenal medulla ganglionic cells 60 days after exposure to detergents].

    PubMed

    Devecerski, V; Marjanov, M; Milićević, S

    1993-01-01

    We investigated histochemical reactions in adrenal medulla sympathic ganglionic cells in the animals who after a 30-day stay in a detergent manufactory department survived 60 days in laboratory conditions. The obtained data show a strong isocytrate dehydrogenase activity in the experimental animals; the reaction to the lactate dehydrogenase activity reflects a decrease of the ganglionic cell volume and a slight decrease of the reaction intensity. The activity of isoenzyme F is mildly increased; similarly was found for isoenzyme S. There was a significant decrease of the succinate dehydrogenase activity--all this was detected in the animals exposed to detergents. Sympathic ganglionic cells within the adrenal medulla are rather sensitive to the influence of detergents. The recovery after the exposure to their toxic effects takes more than 2 months.

  7. Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

    PubMed Central

    Jing, Wei; Liu, Wen-Zhong; Gong, Xin-Wei; Gong, Hai-Qing

    2010-01-01

    Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells’ activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm. PMID:21886670

  8. Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons.

    PubMed Central

    Kosz-Vnenchak, M; Jacobson, J; Coen, D M; Knipe, D M

    1993-01-01

    Thymidine kinase (TK)-negative (TK-) mutant strains of herpes simplex virus type 1 (HSV-1) show reduced expression of alpha and beta viral genes during acute infection of trigeminal ganglion neurons following corneal infection (M. Kosz-Vnenchak, D. M. Coen, and D. M. Knipe, J. Virol. 64:5396-5402, 1990). It was surprising that a defect in a beta gene product would lead to decreased alpha and beta gene expression, given the regulatory pathways demonstrated for HSV infection of cultured cells. In this study, we have examined viral gene expression during reactivation from latent infection in explanted trigeminal ganglion tissue. In explant reactivation studies with wild-type virus, we observed viral productive gene expression over the first 48 h of explant incubation occurring in a temporal order (alpha, beta, gamma) similar to that in cultured cells. This occurred predominantly in latency-associated transcript-positive neurons but was limited to a fraction of these cells. In contrast, TK- mutant viruses showed greatly reduced alpha and beta gene expression upon explant of latently infected trigeminal ganglion tissue. An inhibitor of viral TK or an inhibitor of viral DNA polymerase greatly decreased viral lytic gene expression in trigeminal ganglion tissue latently infected with wild-type virus and explanted in culture. These results indicate that the regulatory mechanisms governing HSV gene expression are different in trigeminal ganglion neurons and cultured cells. We present a new model for viral gene expression in trigeminal ganglion neurons with implications for the nature of the decision process between latent infection and productive infection by HSV. Images PMID:8394454

  9. Percutaneous ultrasound-guided aspiration of an anterior cruciate ligament ganglion cyst: description of technique and case presentation.

    PubMed

    Krill, Michael; Peck, Evan

    2014-12-01

    An anterior cruciate ligament ganglion cyst is an infrequent but potentially clinically significant cause of knee pain. Although the cyst may be removed surgically, percutaneous ultrasound-guided anterior cruciate ligament ganglion cyst aspiration and injection is feasible. To our knowledge, we present the first reported case description of the utilization of ultrasound guidance to perform this procedure with a successful clinical outcome.

  10. Displaced retinal ganglion cells in albino and pigmented rats

    PubMed Central

    Nadal-Nicolás, Francisco M.; Salinas-Navarro, Manuel; Jiménez-López, Manuel; Sobrado-Calvo, Paloma; Villegas-Pérez, María P.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

    2014-01-01

    We have studied in parallel the population of displaced retinal ganglion cells (dRGCs) and normally placed (orthotopic RGCs, oRGCs) in albino and pigmented rats. Using retrograde tracing from the optic nerve, from both superior colliculi (SC) or from the ipsilateral SC in conjunction with Brn3 and melanopsin immunodetection, we report for the first time their total number and topography as well as the number and distribution of those dRGCs and oRGCs that project ipsi- or contralaterally and/or that express any of the three Brn3 isoforms or melanopsin. The total number of RGCs (oRGCs+dRGCs) is 84,706 ± 1249 in albino and 90,440 ± 2236 in pigmented, out of which 2383 and 2428 are melanopsin positive (m-RGCs), respectively. Regarding dRGCs: i/ albino rats have a significantly lower number of dRGCs than pigmented animals (0.5% of the total number of RGCs vs. 2.5%, respectively), ii/ dRGCs project massively to the contralateral SC, iii/ the percentage of ipsilaterality is higher for dRGCs than for oRGCs, iv/ a higher proportion of ipsilateral dRGCs is observed in albino than pigmented animals, v/ dRGC topography is very specific, they predominate in the equatorial temporal retina, being densest where the oRGCs are densest, vi/ Brn3a detects all dRGCs except half of the ipsilateral ones and those that express melanopsin, vii/ the proportion of dRGCs that express Brn3b or Brn3c is slightly lower than in the oRGC population, viii/ a higher percentage of dRGCs (13% albino, 9% pigmented) than oRGCs (2.6%) express melanopsin, ix/ few m-RGCs (displaced and orthotopic) project to the ipsilateral SC, x/ the topography of m-dRGCs does not resemble the general distribution of dRGCs, xi/ The soma size in m-oRGCs ranges from 10 to 21 μm and in m-dRGCs from 8 to 15 μm, xii/ oRGCs and dRGCs have the same susceptibility to axonal injury and ocular hypertension. Although the role of mammalian dRGCs remains to be determined, our data suggest that they are not misplaced by an

  11. Progressive retinal degeneration in ranch mink.

    PubMed

    Hadlow, W J

    1984-01-01

    Retinal degeneration was prevalent in a large group of sapphire and pastel mink (Mustela vison) kept for studies on slow viral diseases. Nearly 78% of those two to eight years old were affected. The retinopathy was equally common in both sexes but more frequent in sapphires (85%) than in pastels (63%), and it was severe more often in sapphires than in pastels. By light microscopy, the primary change appeared to be progressive degeneration of fully developed photoreceptors, beginning in their outer segments. In many mink, including some younger ones, the rods and cones and outer nuclear layer had disappeared from all but the far periphery of the fundus. The inner retinal layers were spared until late in the disease, and the pigment epithelium remained essentially unchanged. The cause of the retinopathy was not established. It may represent an abiotrophy in which the structural integrity of the photoreceptors began to wane in many mink after they reached two years of age. Apart from reducing visual acuity, the retinopathy has implications for the photoperiodic control of fur growth and reproduction in this highly light-sensitive carnivore. PMID:6710807

  12. Iatrogenic corneal perforation in Terrien Marginal Degeneration.

    PubMed

    M R, Kursiah

    2013-04-01

    This case report is about a rare disease with unusual presentation. Failure to recognise atypical presentation may lead to error in managing the patient and cause disastrous complications. Here we highlight a case of Terrien Marginal Degeneration in both eyes with atypical presentation; namely pseudopterygium. A 22 year old man was referred to our centre for iatrogenic right eye corneal perforation after having an atypical pterygium removed at another hospital. On arrival, his vision was 1/60 in both eyes with bilateral cornea Terrien Marginal Degeneration. His right eye anterior chamber was deep with a conjunctival flap covering the perforation site which was located from the 2.30 - 3.30 clock position nasally with no aqueous leak. However after a day his right eye anterior chamber became flat and there was fast aqueous leak from the perforation site. An emergency C shaped peripheral corneal lamellar keratoplasty was performed to seal the perforation. Post operatively his right eye improved to 6/24.

  13. Nodular fasciitis with degeneration and regression.

    PubMed

    Yanagisawa, Akihiro; Okada, Hideki

    2008-07-01

    Nodular fasciitis is a benign reactive proliferation that is frequently misdiagnosed as a sarcoma. This article describes a case of nodular fasciitis of 6-month duration located in the cheek, which degenerated and spontaneously regressed after biopsy. The nodule was fixed to the zygoma but was free from the overlying skin. The mass was 3.0 cm in diameter and demonstrated high signal intensity on T2-weighted magnetic resonance imaging. A small part of the lesion was biopsied. Pathological and immunohistochemical examinations identified the nodule as nodular fasciitis with myxoid histology. One month after the biopsy, the mass showed decreased signal intensity on T2-weighted images and measured 2.2 cm in size. The signal on T2-weighted images showed time-dependent decreases, and the mass continued to reduce in size throughout the follow-up period. The lesion presented as hypointense to the surrounding muscles on T2-weighted images and was 0.4 cm in size at 2 years of follow-up. This case demonstrates that nodular fasciitis with myxoid histology can change to that with fibrous appearance gradually with time, thus bringing about spontaneous regression. Degeneration may be involved in the spontaneous regression of nodular fasciitis with myxoid appearance. The mechanism of regression, unclarified at present, should be further studied. PMID:18650753

  14. Progressive retinal degeneration in ranch mink.

    PubMed

    Hadlow, W J

    1984-01-01

    Retinal degeneration was prevalent in a large group of sapphire and pastel mink (Mustela vison) kept for studies on slow viral diseases. Nearly 78% of those two to eight years old were affected. The retinopathy was equally common in both sexes but more frequent in sapphires (85%) than in pastels (63%), and it was severe more often in sapphires than in pastels. By light microscopy, the primary change appeared to be progressive degeneration of fully developed photoreceptors, beginning in their outer segments. In many mink, including some younger ones, the rods and cones and outer nuclear layer had disappeared from all but the far periphery of the fundus. The inner retinal layers were spared until late in the disease, and the pigment epithelium remained essentially unchanged. The cause of the retinopathy was not established. It may represent an abiotrophy in which the structural integrity of the photoreceptors began to wane in many mink after they reached two years of age. Apart from reducing visual acuity, the retinopathy has implications for the photoperiodic control of fur growth and reproduction in this highly light-sensitive carnivore.

  15. Degenerate parametric oscillation in quantum membrane optomechanics

    NASA Astrophysics Data System (ADS)

    Benito, Mónica; Sánchez Muñoz, Carlos; Navarrete-Benlloch, Carlos

    2016-02-01

    The promise of innovative applications has triggered the development of many modern technologies capable of exploiting quantum effects. But in addition to future applications, such quantum technologies have already provided us with the possibility of accessing quantum-mechanical scenarios that seemed unreachable just a few decades ago. With this spirit, in this work we show that modern optomechanical setups are mature enough to implement one of the most elusive models in the field of open system dynamics: degenerate parametric oscillation. Introduced in the eighties and motivated by its alleged implementability in nonlinear optical resonators, it rapidly became a paradigm for the study of dissipative phase transitions whose corresponding spontaneously broken symmetry is discrete. However, it was found that the intrinsic multimode nature of optical cavities makes it impossible to experimentally study the model all the way through its phase transition. In contrast, here we show that this long-awaited model can be implemented in the motion of a mechanical object dispersively coupled to the light contained in a cavity, when the latter is properly driven with multichromatic laser light. We focus on membranes as the mechanical element, showing that the main signatures of the degenerate parametric oscillation model can be studied in state-of-the-art setups, thus opening the possibility of analyzing spontaneous symmetry breaking and enhanced metrology in one of the cleanest dissipative phase transitions. In addition, the ideas put forward in this work would allow for the dissipative preparation of squeezed mechanical states.

  16. Potent Antiscrapie Activities of Degenerate Phosphorothioate Oligonucleotides

    PubMed Central

    Kocisko, David A.; Vaillant, Andrew; Lee, Kil Sun; Arnold, Kevin M.; Bertholet, Nadine; Race, Richard E.; Olsen, Emily A.; Juteau, Jean-Marc; Caughey, Byron

    2006-01-01

    Although transmissible spongiform encephalopathies (TSEs) are incurable, a key therapeutic approach is prevention of conversion of the normal, protease-sensitive form of prion protein (PrP-sen) to the disease-specific protease-resistant form of prion protein (PrP-res). Here degenerate phosphorothioate oligonucleotides (PS-ONs) are introduced as low-nM PrP-res conversion inhibitors with strong antiscrapie activities in vivo. Comparisons of various PS-ON analogs indicated that hydrophobicity and size were important, while base composition was only minimally influential. PS-ONs bound avidly to PrP-sen but could be displaced by sulfated glycan PrP-res inhibitors, indicating the presence of overlapping binding sites. Labeled PS-ONs also bound to PrP-sen on live cells and were internalized. This binding likely accounts for the antiscrapie activity. Prophylactic PS-ON treatments more than tripled scrapie survival periods in mice. Survival times also increased when PS-ONs were mixed with scrapie brain inoculum. With these antiscrapie activities and their much lower anticoagulant activities than that of pentosan polysulfate, degenerate PS-ONs are attractive new compounds for the treatment of TSEs. PMID:16495266

  17. Evolutionary scenarios for double degenerate systems

    NASA Astrophysics Data System (ADS)

    Sarna, M. J.; Marks, P. B.; Connon Smith, Robert

    1996-03-01

    We propose evolutionary scenarios in which double degenerate white dwarf systems can be produced through one or two phases of stable mass transfer. We consider Algol-type evolution as well as evolution involving first a stage of common-envelope (CE) evolution followed by a phase of stable mass transfer. We also show that the final orbital period of double white dwarf systems depends on the period after the first phase of mass transfer, and that there is critical period (the bifurcation period) above which systems evolve to orbital periods of the order of days and below which systems evolve towards very short orbital periods (a few hours). This probably corresponds to the observation that double degenerate systems have periods either of hours or of days. We also find a limit on the stability of mass transfer for systems that first go through a phase of CE evolution. We suggest that our new evolutionary scheme involving two stages of stable mass transfer and our scheme involving first CE evolution followed by stable mass transfer should be included in population synthesis models.

  18. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

  19. [Acquired polycystic degeneration of the kidneys].

    PubMed

    Kreisel-Büstgens, C; Büstgens, L; Graben, N

    1990-12-15

    Kidneys of patients with advanced renal insufficiency undergo polycystic transformation, described as acquired cystic degeneration (ACD). In 118 chronic dialysis patients clinical data were compared with sonographic findings of their 221 cirrhotic kidneys: 74 (63%) patients showed distinctly discernible renal cysts: 19 patients hat one single cyst, nine patients had two to eight cysts, 46 patients had more than eight cysts. Accordingly 39% of patients had ACD. Cystic transformation was of the same degree on both sides and in a few cases so marked that a formal discrimination to congenital cystic disease seemed impossible. Cystic degeneration was not influenced by patient's age, sex or underlying renal disease, but was dependent on the duration of both, renal disease and dialysis treatment. After eight years 71% of dialysis patients had ACD. In coincidence with cystic transformation the size of the kidneys apparently normalized and Hb-concentration rose from 8 to 10 g/dl. Complications were seen in six patients: two severe retroperitoneal bleedings and four hypernephroma were observed. The etiology of cystic transformation and its possible role as precancerosis are discussed.

  20. Chemical ablation of stellate ganglion for head and neck cancer pain.

    PubMed

    Ghai, A; Kaushik, T; Kumar, R; Wadhera, S

    2016-01-01

    We present a case of patient with orofacial cancer having pain on one side of face affecting her ability to speak, chew, swallow and sleep leading to emotional and behavioral deterioration. A diagnostic stellate ganglion block was performed followed by chemical neurolysis using phenol under ultrasound guidance, to prevent complications due to inadvertent spread of drug. Her pain scores decreased drastically, she was able to chew and swallow. Weighing the risk of permanent Horner's syndrome or motor paralysis with benefit of improvement in basic functioning of debilitated patients chemical neurolysis of stellate ganglion can be performed with advanced imaging modalities. PMID:27363209

  1. The relation between resolution measurements and numbers of retinal ganglion cells in the same human subjects.

    PubMed

    Popovic, Zoran; Sjöstrand, Johan

    2005-08-01

    Limiting factors of resolution have previously only been investigated by using resolution data and retinal ganglion cell spacing data from different individuals. We report on our unique opportunity to study the intra-individual relationship in three human subjects between retinal ganglion cell separations and resolution thresholds, measured with high-pass resolution perimetry. Our data show that resolution is directly proportional to half the midget population, in accordance with the hypothesis that a dichotomous midget ON/OFF population mediates resolution. PMID:15924946

  2. Encephalomyeloneuropathy with ganglionitis of the myenteric plexuses in the absence of cancer.

    PubMed

    Horoupian, D S; Kim, Y

    1982-06-01

    A 55-year-old woman presented with rapidly progressive brainstem dysfunction which led to death within a month. She also had constipation for three weeks, and barium enema showed ileus. Subacute encephalomyelitis predominantly involving the medulla and pons correlated with the patient's initial symptoms. In addition, ganglionitis of the myenteric plexuses explained the constipation and ileus. Ganglioradiculoneuropathy was another finding. The presence of abundant neuronophagia in the brainstem, dorsal root ganglia, and myenteric plexuses raised the speculation that a putative virus, toxic agent, or immune reaction possessed special affinity for neurons and ganglion cells. The neuropathological findings were similar to paraneoplastic changes, but no neoplasm was found.

  3. FMRFamide-like immunoreactivity in the ventral ganglion of the fly Sarcophaga bullata: metamorphic changes.

    PubMed

    Sivasubramanian, P

    1991-01-01

    1. Localization of FMRFamide-like immunoreactivity was examined in the ventral ganglion of the fly Sarcophaga bullata using the indirect immunofluorescent method. 2. There are six large cells in the thoracic ganglion which are highly immunoreactive at all stages of development. 3. During metamorphosis the thoracic FLI neurons shift their position from ventrolateral to mid-ventral position and their axons terminate and elaborate a highly immunoreactive dorsal neural sheath. 4. It is suggested that the dorsal neural sheath may function as a neurohaemal organ from which FMRFamide-like substances may be released into the haemolymph to act as neurohormones.

  4. Mechanisms of axon degeneration: from development to disease.

    PubMed

    Saxena, Smita; Caroni, Pico

    2007-10-01

    Axon degeneration is an active, tightly controlled and versatile process of axon segment self-destruction. Although not involving cell death, it resembles apoptosis in its logics. It involves three distinct steps: induction of competence in specific neurons, triggering of degeneration at defined axon segments of competent neurons, and rapid fragmentation and removal of the segments. The mechanisms that initiate degeneration are specific to individual settings, but the final pathway of pruning is shared; it involves microtubule disassembly, axon swellings, axon fragmentation, and removal of the remnants by locally recruited phagocytes. The tight regulatory properties of axon degeneration distinguish it from passive loss phenomena, and confer significance to processes that involve it. Axon degeneration has prominent roles in development, upon lesions and in disease. In development, it couples the progressive specification of neurons and circuits to the removal of defined axon branches. Competence might involve transcriptional switches, and local triggering can involve axon guidance molecules and synaptic activity patterns. Lesion-induced Wallerian degeneration is inhibited in the presence of Wld(S) fusion protein in neurons; it involves early local, and later, distal degeneration. It has recently become clear that like in other settings, axon degeneration in disease is a rapid and specific process, which should not be confused with a variety of disease-related pathologies. Elucidating the specific mechanisms that initiate axon degeneration should open up new avenues to investigate principles of circuit assembly and plasticity, to uncover mechanisms of disease progression, and to identify ways of protecting synapses and axons in disease.

  5. A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells

    PubMed Central

    RAYMOND, IONA D.; POOL, ANGELA L.; VILA, ALEJANDRO; BRECHA, NICHOLAS C.

    2013-01-01

    A DBA/2J (D2) transgenic mouse line with cyan fluorescent protein (CFP) reporter expression in ganglion cells was developed for the analysis of ganglion cells during progressive glaucoma. The Thy1-CFP D2 (CFP-D2) line was created by congenically breeding the D2 line, which develops pigmentary glaucoma, and the Thy1-CFP line, which expresses CFP in ganglion cells. Microsatellite marker analysis of CFP-D2 progeny verified the genetic inclusion of the D2 isa and ipd loci. Specific mutations within these loci lead to dysfunctional melanosomal proteins and glaucomatous phenotype in D2 mice. Polymerase chain reaction analysis confirmed the inclusion of the Thy1-CFP transgene. CFP-fluorescent ganglion cells, 6–20 μm in diameter, were distributed in all retinal regions, CFP processes were throughout the inner plexiform layer, and CFP-fluorescent axons were in the fiber layer and optic nerve head. Immunohistochemistry with antibodies to ganglion cell markers NF-L, NeuN, Brn3a, and SMI32 was used to confirm CFP expression in ganglion cells. Immunohistochemistry with antibodies to amacrine cell markers HPC-1 and ChAT was used to confirm weak CFP expression in cholinergic amacrine cells. CFP-D2 mice developed a glaucomatous phenotype, including iris disease, ganglion cell loss, attrition of the fiber layer, and elevated intraocular pressure. A CFP-D2 transgenic line with CFP-expressing ganglion cells was developed, which has (1) a predominantly D2 genetic background, (2) CFP-expressing ganglion cells, and (3) age-related progressive glaucoma. This line will be of value for experimental studies investigating ganglion cells and their axons in vivo and in vitro during the progressive development of glaucoma. PMID:19930759

  6. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells.

    PubMed

    Gaub, Benjamin M; Berry, Michael H; Holt, Amy E; Reiner, Andreas; Kienzler, Michael A; Dolgova, Natalia; Nikonov, Sergei; Aguirre, Gustavo D; Beltran, William A; Flannery, John G; Isacoff, Ehud Y

    2014-12-23

    Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0(460) in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.

  7. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells

    PubMed Central

    Gaub, Benjamin M.; Berry, Michael H.; Holt, Amy E.; Reiner, Andreas; Kienzler, Michael A.; Dolgova, Natalia; Nikonov, Sergei; Aguirre, Gustavo D.; Beltran, William A.; Flannery, John G.; Isacoff, Ehud Y.

    2014-01-01

    Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0460). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0460 was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0460 was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0460 in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0460 in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0460 was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation. PMID:25489083

  8. Degenerate polygonal tilings in simple animal tissues

    NASA Astrophysics Data System (ADS)

    Hočevar, A.; Ziherl, P.

    2009-07-01

    The salient feature of one-cell-thick epithelia is their en face view, which reveals the polygonal cross section of the close-packed prismatic cells. The physical mechanisms that shape these tissues were hitherto explored using theories based on cell proliferation, which were either entirely topological or included certain morphogenetic forces. But mitosis itself may not be instrumental in molding the tissue. We show that the structure of simple epithelia can be explained by an equilibrium model where energy-degenerate polygons in an entropy-maximizing tiling are described by a single geometric parameter encoding their inflatedness. The two types of tilings found numerically—ordered and disordered—closely reproduce the patterns observed in Drosophila, Hydra, and Xenopus and they generalize earlier theoretical results. Free of a specific cell self-energy, cell-cell interaction, and cell division kinetics, our model provides an insight into the universality of living and inanimate two-dimensional cellular structures.

  9. Solitons in Degenerate Electron-Phonon Systems

    NASA Astrophysics Data System (ADS)

    Foell, Charles; Clougherty, Dennis

    2004-03-01

    We consider a 1øplus 1-dimensional model describing the coupling between degenerate electron states under local Jahn-Teller interactions. In the adiabatic approximation, the equations of motion are shown to reduce to a set of coupled non-linear Schrödinger equations in the electron fields. We demonstrate that in the continuum limit solitary waves of the wave-daughter wave type are stable for sufficiently strong on-site Coulomb repulsion. Our results may have relevance to describing the electronic and optical properties of quasi-one-dimensional systems such as halogen-bridged mixed-valence transition-metal linear-chain complexes (MX chains) and polymeric fullerides.

  10. Subwavelength total acoustic absorption with degenerate resonators

    NASA Astrophysics Data System (ADS)

    Yang, Min; Meng, Chong; Fu, Caixing; Li, Yong; Yang, Zhiyu; Sheng, Ping

    2015-09-01

    We report the experimental realization of perfect sound absorption by sub-wavelength monopole and dipole resonators that exhibit degenerate resonant frequencies. This is achieved through the destructive interference of two resonators' transmission responses, while the matching of their averaged impedances to that of air implies no backscattering, thereby leading to total absorption. Two examples, both using decorated membrane resonators (DMRs) as the basic units, are presented. The first is a flat panel comprising a DMR and a pair of coupled DMRs, while the second one is a ventilated short tube containing a DMR in conjunction with a sidewall DMR backed by a cavity. In both examples, near perfect absorption, up to 99.7%, has been observed with the airborne wavelength up to 1.2 m, which is at least an order of magnitude larger than the composite absorber. Excellent agreement between theory and experiment is obtained.

  11. Quantum Walk in Degenerate Spin Environments

    NASA Astrophysics Data System (ADS)

    Carlström, Johan; Prokof'ev, Nikolay; Svistunov, Boris

    2016-06-01

    We study the propagation of a hole in degenerate (paramagnetic) spin environments. This canonical problem has important connections to a number of physical systems, and is perfectly suited for experimental realization with ultracold atoms in an optical lattice. At the short-to-intermediate time scale that we can access using a stochastic-series-type numeric scheme, the propagation turns out to be distinctly nondiffusive with the probability distribution featuring minima in both space and time due to quantum interference, yet the motion is not ballistic, except at the beginning. We discuss possible scenarios for long-term evolution that could be explored with an unprecedented degree of detail in experiments with single-atom resolved imaging.

  12. [Epidemiology of age-related macular degeneration].

    PubMed

    Brandl, C; Stark, K J; Wintergerst, M; Heinemann, M; Heid, I M; Finger, R P

    2016-09-01

    Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies. PMID:27541733

  13. Responses to light after retinal degeneration.

    PubMed

    Mrosovsky, N; Salmon, P A; Foster, R G; McCall, M A

    2000-01-01

    Transgenic rodless mice were given 1-h pulses of light of varying brightness at times of the night when they were normally active. The rodless mice showed decreases in locomotor activity during light pulses brighter than 2 lux; these decreases were significantly greater than those in wildtypes (ANOVA, P < 0.01). However, with very dim light, rodless mice showed no changes in activity, whereas wildtype mice actually increased their activity. It is suggested that irradiance detection could be enhanced by absence of image-forming vision. Enhanced inhibition of activity around twilight may be adaptive for mice in some circumstances and so help maintain genes for retinal degeneration in natural populations. PMID:10824261

  14. A computational model of motor neuron degeneration.

    PubMed

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

    2014-08-20

    To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations.

  15. Mapping cerebellar degeneration in HIV/AIDS.

    PubMed

    Klunder, Andrea D; Chiang, Ming-Chang; Dutton, Rebecca A; Lee, Sharon E; Toga, Arthur W; Lopez, Oscar L; Aizenstein, Howard J; Becker, James T; Thompson, Paul M

    2008-11-19

    Progressive brain atrophy in HIV/AIDS is associated with impaired psychomotor performance, perhaps partly reflecting cerebellar degeneration; yet little is known about how HIV/AIDS affects the cerebellum. We visualized the three-dimensional profile of atrophy in 19 HIV-positive patients (age: 42.9+/-8.3 years) versus 15 healthy controls (age: 38.5+/-12.0 years). We localized consistent patterns of subregional atrophy with an image analysis method that automatically deforms each patient's scan, in three dimensions, to match a reference image. Atrophy was greatest in the posterior cerebellar vermis (14.9% deficit) and correlated with depression severity (P=0.009, corrected), but not with dementia, alcohol/substance abuse, CD4+T-cell counts, or viral load. Profound cerebellar deficits in HIV/AIDS (P=0.007, corrected) were associated with depression, suggesting a surrogate disease marker for antiretroviral trials.

  16. Degenerate R-S perturbation theory

    NASA Technical Reports Server (NTRS)

    Hirschfelder, J. O.; Certain, P. R.

    1973-01-01

    A concise, systematic procedure is given for determining the Rayleigh-Schrodinger energies and wave functions of degenerate states to arbitrarily high orders even when the degeneracies of the various states are resolved in arbitrary orders. The procedure is expressed in terms of an iterative cycle in which the energy through the (2n+1)st order is expressed in terms of the partially determined wave function through the n-th order. Both a direct and an operator derivation are given. The two approaches are equivalent and can be transcribed into each other. The direct approach deals with the wave functions (without the use of formal operators) and has the advantage that it resembles the usual treatment of nondegenerate perturbations and maintains close contact with the basic physics. In the operator approach, the wave functions are expressed in terms of infinite order operators which are determined by the successive resolution of the space of the zeroth order functions.

  17. Age-related macular degeneration: current treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

  18. Crystallization and collapse in relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2013-04-15

    In this paper, it is shown that a mass density limit exists beyond which the relativistically degenerate matter would crystallize. The mass density limit, found here, is quite analogous to the mass limit predicted by Chandrasekhar for a type of compact stars called white dwarfs (M{sub Ch} Asymptotically-Equal-To 1.43 Solar Mass). In this study, the old problem of white dwarf core collapse, which has been previously investigated by Chandrasekhar using hydrostatic stability criteria, is revisited in the framework of the quantum hydrodynamics model by inspection of the charge screening at atomic scales in the relativistic degeneracy plasma regime taking into account the relativistic Fermi-Dirac statistics and electron interaction features such as the quantum statistical pressure, Coulomb attraction, electron exchange-correlation, and quantum recoil effects. It is revealed that the existence of ion correlation and crystallization of matter in the relativistically degenerate plasma puts a critical mass density limit on white dwarf core region. It is shown that a white dwarf star with a core mass density beyond this critical limit can undergo the spontaneous core collapse (SCC). The SCC phenomenon, which is dominantly caused by the electron quantum recoil effect (interference and localization of the electron wave function), leads to a new exotic state of matter. In such exotic state, the relativistic electron degeneracy can lead the white dwarf crystallized core to undergo the nuclear fusion and an ultimate supernova by means of the volume reduction (due to the enhanced compressibility) and huge energy release (due to the increase in cohesive energy), under the stars huge inward gravitational pressure. Moreover, it is found that the SCC phenomenon is significantly affected by the core composition (it is more probable for heavier plasmas). The critical mass density found here is consistent with the values calculated for core density of typical white dwarf stars.

  19. Retrograde Axonal Degeneration in Parkinson Disease

    PubMed Central

    Tagliaferro, Patricia; Burke, Robert E.

    2016-01-01

    In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics. PMID:27003783

  20. Macroanatomical investigation of the aorticorenal ganglion in 1-day-old infant sheep.

    PubMed

    Klećkowska-Nawrot, J; Kaczyńska, K; Jakubowska, W

    2009-06-01

    The aorticorenal gland belongs to the paired splanchnic ganglion, which is the main component of the coeliac plexus. It lies near the renal artery and suprarenal gland. The research was conducted on 13 1-day-old infant sheep - eight males and five females. Based on the conducted studies, it was concluded that the aorticorenal ganglion is characterized by the variable location in relation to the abdominal aorta, renal artery, caudal vena cava and suprarenal gland (holotopy), the thoracic and lumbar segment of the vertebral column (skeletotopy) (between L(1) and L(3)) and also a different shape (elongated, round, triangular, oval) as well as variable length (the aorticorenal ganglion is longer on the left side of the body; 2.72 mm) and distance from the caudal end of the suprarenal gland (longer on the left side of the body; 8.34 mm). With regard to the sex of the animal, the ganglion is the longest on the left side in ewes (3.02 mm), while in rams it is the longest on the right side (2.68 mm). Regarding the division according to sex, the longest segment was observed on the right side in ewes (9.27 mm), and the shortest segment in rams was also on the right side (6.84 mm).

  1. Contribution of the GABAergic pathway(s) to the correlated activities of chicken retinal ganglion cells.

    PubMed

    Liu, Xue; Zhou, Yi; Gong, Hai-Qing; Liang, Pei-Ji

    2007-10-26

    In the present study, the spatiotemporal pattern of chicken retinal ganglion cells' firing activity in response to full-field white light stimulation was investigated. Cross-correlation analysis showed that ganglion cells of sustained subtype fired in precise synchrony with their adjacent neurons of the same subtype (delay lag within 2 ms, narrow correlation). On the other hand, the activities of neighboring ganglion cells of transient subtype were correlated with distributed time lags (10-30 ms, medium correlation). Pharmacological studies demonstrated that the intensity of the medium correlations could be strengthened when exogenous GABA was applied and attenuated when GABA receptors were blocked by picrotoxin. Meanwhile, the GABAergic modulation on the narrow correlations was not consistent. These results suggest that, in the chicken retina, GABAergic pathway(s) are likely involved in the formation of medium correlations between ganglion cells. Neurons might fire at a lower rate but with higher level of synchronization to improve the efficiency of information transmission, with the mechanism involving the GABAergic inhibitory input. PMID:17919471

  2. Ganglion cell distribution and retinal resolution in the Florida manatee, Trichechus manatus latirostris.

    PubMed

    Mass, Alla M; Ketten, Darlene R; Odell, Daniel K; Supin, Alexander Ya

    2012-01-01

    The topographic organization of retinal ganglion cells was examined in the Florida manatee (Trichechus manatus latirostris) to assess ganglion cell size and distribution and to estimate retinal resolution. The ganglion cell layer of the manatee's retina was comprised primarily of large neurons with broad intercellular spaces. Cell sizes varied from 10 to 60 μm in diameter (mean 24.3 μm). The retinal wholemounts from adult animals measured 446-501 mm(2) in area with total ganglion cell counts of 62,000-81,800 (mean 70,200). The cell density changed across the retina, with the maximum in the area below the optic disc and decreasing toward the retinal edges and in the immediate vicinity of the optic disc. The maximum cell density ranged from 235 to 337 cells per millimeter square in the adult retinae. Two wholemounts obtained from juvenile animals were 271 and 282 mm(2) in area with total cell numbers of 70,900 and 68,700, respectively (mean 69,800), that is, nearly equivalent to those of adults, but juvenile retinae consequently had maximum cell densities that were higher than those of adults: 478 and 491 cells per millimeter square. Calculations indicate a retinal resolution of ∼19' (1.6 cycles per degree) in both adult and juvenile retinae.

  3. Expression of squid iridescence depends on environmental luminance and peripheral ganglion control.

    PubMed

    Gonzalez-Bellido, P T; Wardill, T J; Buresch, K C; Ulmer, K M; Hanlon, R T

    2014-03-15

    Squid display impressive changes in body coloration that are afforded by two types of dynamic skin elements: structural iridophores (which produce iridescence) and pigmented chromatophores. Both color elements are neurally controlled, but nothing is known about the iridescence circuit, or the environmental cues, that elicit iridescence expression. To tackle this knowledge gap, we performed denervation, electrical stimulation and behavioral experiments using the long-fin squid, Doryteuthis pealeii. We show that while the pigmentary and iridescence circuits originate in the brain, they are wired differently in the periphery: (1) the iridescence signals are routed through a peripheral center called the stellate ganglion and (2) the iridescence motor neurons likely originate within this ganglion (as revealed by nerve fluorescence dye fills). Cutting the inputs to the stellate ganglion that descend from the brain shifts highly reflective iridophores into a transparent state. Taken together, these findings suggest that although brain commands are necessary for expression of iridescence, integration with peripheral information in the stellate ganglion could modulate the final output. We also demonstrate that squid change their iridescence brightness in response to environmental luminance; such changes are robust but slow (minutes to hours). The squid's ability to alter its iridescence levels may improve camouflage under different lighting intensities.

  4. Post-Ganglionic Horner's Syndrome: An Unusual Presentation of Non-Hodgkin Lymphoma

    PubMed Central

    Ruiz e Resende, Lucilene Silva; Gaiolla, Rafael Dezen; Niéro-Melo, Lígia; Custódio Domingues, Maria Aparecida; de Lima Resende, Luiz Antônio

    2012-01-01

    In this paper, we present the rare case of a patient with cervical lymphadenopathy diagnosed as a T-cell-rich B-cell non-Hodgkin lymphoma that manifested Horner's syndrome due to a post-ganglionic sympathetic neuron lesion caused by the tumor. PMID:22611367

  5. Effects of axotomy or target atrophy on membrane properties of rat sympathetic ganglion cells.

    PubMed Central

    Sánchez-Vives, M V; Gallego, R

    1993-01-01

    1. The electrical properties of rat superior cervical ganglion cells were examined in vitro with intracellular microelectrodes after axotomy or atrophy of the submandibular salivary gland. 2. Membrane time constant, input resistance and excitatory synaptic potentials (EPSPs) were decreased to about 50% of their control values 7-10 days after axotomy. 3. Axotomized ganglion cells also showed reduced action potentials and after-hyperpolarizations (AHPs). The AHP duration was reduced to 40% of the control value. 4. In 25% of the axotomized cells, the action potential was followed by an after-depolarization (ADP) instead of the AHP that was always present in control cells. In eleven out of seventeen axotomized cells with ADP, preganglionic stimulation failed to evoke an EPSP, whereas the failure of the synaptic response was never observed in control cells and occurred only in two of fifty-three axotomized cells with AHP. 5. In some axotomized cells with AHP, a depolarizing potential developed after a train of action potentials. This was never observed in control cells. 6. Sympathetic neurones innervating the submandibular gland in control animals had membrane properties similar to those observed in other ganglion cells. 7. The properties of neurones innervating the submandibular gland remained unaltered after the experimentally induced atrophy of the gland. 8. It is concluded that the marked effects of short-term axotomy on membrane properties of sympathetic ganglion cells are not reproduced by long-term atrophy of the target tissue. PMID:8120834

  6. Ocular anatomy, ganglion cell distribution and retinal resolution of a killer whale (Orcinus orca).

    PubMed

    Mass, Alla M; Supin, Alexander Y; Abramov, Andrey V; Mukhametov, Lev M; Rozanova, Elena I

    2013-01-01

    Retinal topography, cell density and sizes of ganglion cells in the killer whale (Orcinus orca) were analyzed in retinal whole mounts stained with cresyl violet. A distinctive feature of the killer whale's retina is the large size of ganglion cells and low cell density compared to terrestrial mammals. The ganglion cell diameter ranged from 8 to 100 µm, with the majority of cells within a range of 20-40 µm. The topographic distribution of ganglion cells displayed two spots of high cell density located in the temporal and nasal quadrants, 20 mm from the optic disk. The high-density areas were connected by a horizontal belt-like area passing below the optic disk of the retina. Peak cell densities in these areas were evaluated. Mean peak cell densities were 334 and 288 cells/mm(2) in the temporal and nasal high-density areas, respectively. With a posterior nodal distance of 19.5 mm, these high-density data predict a retinal resolution of 9.6' (3.1 cycles/deg.) and 12.6' (2.4 cycles/deg.) in the temporal and nasal areas, respectively, in water. PMID:23018493

  7. Ocular anatomy, ganglion cell distribution and retinal resolution of a killer whale (Orcinus orca).

    PubMed

    Mass, Alla M; Supin, Alexander Y; Abramov, Andrey V; Mukhametov, Lev M; Rozanova, Elena I

    2013-01-01

    Retinal topography, cell density and sizes of ganglion cells in the killer whale (Orcinus orca) were analyzed in retinal whole mounts stained with cresyl violet. A distinctive feature of the killer whale's retina is the large size of ganglion cells and low cell density compared to terrestrial mammals. The ganglion cell diameter ranged from 8 to 100 µm, with the majority of cells within a range of 20-40 µm. The topographic distribution of ganglion cells displayed two spots of high cell density located in the temporal and nasal quadrants, 20 mm from the optic disk. The high-density areas were connected by a horizontal belt-like area passing below the optic disk of the retina. Peak cell densities in these areas were evaluated. Mean peak cell densities were 334 and 288 cells/mm(2) in the temporal and nasal high-density areas, respectively. With a posterior nodal distance of 19.5 mm, these high-density data predict a retinal resolution of 9.6' (3.1 cycles/deg.) and 12.6' (2.4 cycles/deg.) in the temporal and nasal areas, respectively, in water.

  8. Infrared-sensitive pit organ and trigeminal ganglion in the crotaline snakes

    PubMed Central

    2011-01-01

    The infrared (IR) receptors in the pit organ of crotaline snakes are very sensitive to temperature. The sensitivity to IR radiation is much greater in crotaline snakes than in boid snakes because they have a thermosensitive membrane suspended in a pair of pits that comprise the pit organ. The vasculature of the pit membrane, which is located near IR-sensitive terminal nerve masses, the IR receptors, supplies the blood necessary to provide cooling and the energy and oxygen that the IR receptors require. The ophthalmic and maxillary branches of the trigeminal nerve innervate the pit membrane. In crotaline snakes, the trigeminal ganglion (TG) is divided into the ophthalmic and maxillomandibular ganglia; a prominent septum further separates the two divisions of the maxillomandibular ganglion. The TG neurons in the ophthalmic ganglion and the maxillary division of the maxillomandibular ganglion relay IR sensation to the brain. This article reviews the IR-sensitive pit organ and trigeminal sensory system structures in crotaline snakes. PMID:21519544

  9. Ganglion cell distribution and retinal resolution in the Florida manatee, Trichechus manatus latirostris.

    PubMed

    Mass, Alla M; Ketten, Darlene R; Odell, Daniel K; Supin, Alexander Ya

    2012-01-01

    The topographic organization of retinal ganglion cells was examined in the Florida manatee (Trichechus manatus latirostris) to assess ganglion cell size and distribution and to estimate retinal resolution. The ganglion cell layer of the manatee's retina was comprised primarily of large neurons with broad intercellular spaces. Cell sizes varied from 10 to 60 μm in diameter (mean 24.3 μm). The retinal wholemounts from adult animals measured 446-501 mm(2) in area with total ganglion cell counts of 62,000-81,800 (mean 70,200). The cell density changed across the retina, with the maximum in the area below the optic disc and decreasing toward the retinal edges and in the immediate vicinity of the optic disc. The maximum cell density ranged from 235 to 337 cells per millimeter square in the adult retinae. Two wholemounts obtained from juvenile animals were 271 and 282 mm(2) in area with total cell numbers of 70,900 and 68,700, respectively (mean 69,800), that is, nearly equivalent to those of adults, but juvenile retinae consequently had maximum cell densities that were higher than those of adults: 478 and 491 cells per millimeter square. Calculations indicate a retinal resolution of ∼19' (1.6 cycles per degree) in both adult and juvenile retinae. PMID:21964938

  10. Characterization of a putative acetylcholine receptor in chick ciliary ganglion neurons

    SciTech Connect

    Stollberg, J.

    1985-01-01

    Monoclonal antibodies to the main immunogenic region on the alpha subunit of acetylcholine receptors in muscle and electric organ recognize membrane components in chick brain and ciliary ganglia that are candidates for the neuronal receptor. The component in chick brain has been purified by immunoaffinity chromatography. It specifically binds nicotine but not alpha-bungarotoxin, and can be affinity labeled with (/sup 3/H)bromoacetylcholine. The cross-reacting component in ciliary ganglion neurons is concentrated in synaptic membrane, and can be modulated by exposure of the cells to cholinergic ligands in culture. The cross-reacting component in ciliary ganglion neurons is an integral membrane component that binds concanavalin A, and it is distinct from the alpha-bungarotoxin binding component. The acetylcholine receptor function in these neurons can be locked by affinity alkylation with bromoacetylcholine, indicating similarity in this respect to receptors from muscle and electric organ. Antisera raised against the partially purified component from chick brain also block receptor function on ciliary ganglion neurons. The subcellular distribution of the ganglion component in culture is assessed, and it is shown that approximately 2/3 of the cross-reacting components are intracellular; the majority of these seem not to be destined for insertion into the plasma membrane.

  11. Activity of retinal ganglion cells following intense, nanosecond laser flashes. Final report, 1983-1986

    SciTech Connect

    Glickman, R.D.

    1989-01-01

    The effects of intense, but nonlesion-producing, laser exposures of 20-ns duration were determined on the light responses and spontaneous activity of retinal ganglion cells recorded in situ from the rhesus monkey. (Following a single, 20-ns exposure centered on its receptive field, a ganglion cell produced an 'afterdischarge' of maintained action potentials). The duration of the afterdischarge depended on the diameter of the laser beam on the retina and on the beam's intensity. Laser exposures subtending 0.5 to 2.0 deg, and delivering 45 to 60% of the maximum permissible exposure, elicited afterdischarges that lasted up to 80 s. When the beam diameter was decreased to 0.25 deg, the afterdischarge was reduced to 30 s, and to less than 5 s with the 0.12-deg beam. Light sensitivity after the laser exposure recovered rapidly during the first 10 s and then more slowly, but exponentially, until it reached the preflash level. Color-opponent ganglion cells exhibited a phenomenon called 'response-reversal' after the laser exposure, presumably due to selective adaptation of a mid-wavelength cone-input. Because a 20-ns exposure, regardless of intensity, is likely to photoregenerate more than half of the available visual pigment, the effects of ganglion cell response described here are not likely to be due solely to pigment bleaching.

  12. Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion

    PubMed Central

    Richter, H.; Bruderer, T.; Goldenberger, D.; Emonet, S.; Strahm, C.

    2015-01-01

    Neisseria cinerea is a human commensal. The first known case of meningitis and bacteremia due to Neisseria cinerea following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed. PMID:26511743

  13. Expression of pro-opiomelanocortin (POMC) in the cerebral ganglion and ovary of a protochordate.

    PubMed

    Masini, M A; Sturla, M; Gallinelli, A; Candiani, S; Facchinetti, F; Pestarino, M

    1998-01-01

    The distribution of neurones expressing POMC mRNA in the cerebral ganglion of the protochordate ascidian, Styela plicata, was investigated using a non-radioactive in situ hybridization technique. Nerve cell bodies of mono and bipolar types expressing POMC mRNA, were observed mainly in the outer layer of the ganglion. Discrete groups of neurones containing POMC mRNA were also localized in the inner portion of the ganglion, and few small monopolar perykaria expressing POMC mRNA were visible at the emergence of the main nerve trunks. POMC mRNA labeling was also found at level of the cytoplasm of previtellogenic and vitellogenic oocytes, and of follicular cells. Our results demonstrate the expression of one or more genes in the cerebral ganglion and ovary, that may be similar to one or more regions of the mammalian POMC gene. Therefore POMC-related molecules seem to be involved in neuromodulatory pathways and regulatory mechanisms of the oogenesis of ascidians.

  14. Expression of zinc transporter ZnT7 in mouse superior cervical ganglion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The superior cervical ganglion (SCG) neurons contain a considerable amount of zinc ions, but little is known about zinc homeostasis in the SCG. It is known that zinc transporter 7 (ZnT7, Slc30a7), a member of the Slc30 ZnT family, is involved in mobilizing zinc ions from the cytoplasm into the Golgi...

  15. Transient structures of the human fetal brain: subplate, thalamic reticular complex, ganglionic eminence.

    PubMed

    Ulfig, N; Neudörfer, F; Bohl, J

    2000-07-01

    Morphological features of the subplate, the thalamic reticular complex and the ganglionic eminence, which represent three major transient structures of the human fetal forebrain, are summarized with special reference to their functional roles. The subplate harboring various neuronal types is an outstandingly wide zone subjacent to the cortical plate in the human fetal brain. Within the subplate various cortical afferents establish synaptic contacts for a prolonged period before entering the cortical plate. Therefore, the subplate is regarded as a "waiting compartment" which is required for the formation of mature cortical connections. Next to the thalamic reticular nucleus, within the fibers of internal capsule, the perireticular nucleus is located which has been established as a distinct entity during development. Its various neuronal types express a number of different neuroactive substances. Perinatally, the perireticular nucleus is drastically reduced in size. It is involved in the guidance of corticofugal and thalamocortical fibers. The ganglionic eminence is a conspicuous proliferative area that persists throughout nearly the entire fetal period. In the human fetal brain it extends medially upon the dorsal thalamic nuclei which receive precursor cells from the ganglionic eminence. Postmitotic cells in the marginal zone of the ganglionic eminence serve as an intermediate target for growing axons. On the whole, all three structures establish transient neural circuitries that may be essential for the formation of adult projections. The characteristics of the three transient structures are particularly relevant for developmental neuropathology as these structures may be damaged in disorders that preferentially occur in preterm infants. PMID:10963122

  16. Chronic intestinal pseudo-obstruction in a horse: a case of myenteric ganglionitis.

    PubMed

    Chénier, Sonia; Macieira, Susana M; Sylvestre, Doris; Jean, Daniel

    2011-04-01

    An 11-year-old Quarter horse mare was presented for recurrent episodes of colic. A chronic intestinal pseudo-obstruction was diagnosed. Medical treatment and surgical resection of the colon were performed but the condition did not improve and the horse was euthanized. Histopathological examination revealed a myenteric ganglionitis of the small intestine and ascending colon.

  17. Autonomic ganglionitis with severe hypertension, migraine, and episodic but fatal hypotension.

    PubMed

    Lee, H C; Coulter, C L; Adickes, E D; Porterfield, J; Robertson, D; Bravo, E; Pettinger, W A

    1996-09-01

    We report the clinical, pathologic, and immunohistochemical features of a severe hypertensive patient with recurrent migraine-induced hypotension. The patient died of migraine-induced vasomotor paralysis despite prompt institutions of fluid and sympathomimetic and parasympatholytic agents. Postmortem study revealed autonomic ganglionitis and neuritis.

  18. Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion.

    PubMed

    von Kietzell, M; Richter, H; Bruderer, T; Goldenberger, D; Emonet, S; Strahm, C

    2016-01-01

    Neisseria cinerea is a human commensal. The first known case of meningitis and bacteremia due to Neisseria cinerea following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed.

  19. A minute fraction of Syrian golden hamster retinal ganglion cells project bilaterally.

    PubMed

    Hsiao, K; Sachs, G M; Schneider, G E

    1984-02-01

    Bilaterally projecting retinal ganglion cells (BPRGCs) in the adult Syrian golden hamster were identified through the use of two retrogradely transported neuronal labels, horseradish peroxidase and Nuclear Yellow, placed separately in each optic tract. The distribution and size of doubly labeled retinal ganglion cells were characterized and their numbers were determined. Strict criteria were used to exclude artifactual doubly labeled cells. This work revealed that: (a) BPRGCs comprise less than 0.01% of the entire retinal ganglion cell population, averaging 7.4 (SD = 3) cells per retina; (b) BPRGCs are found primarily in the upper, peripheral retina and not along the vertical meridian or in the temporal crescent; and (c) BPRGCs correspond in size to ordinary retinal ganglion cells in their immediate vicinity, thus providing no evidence that they comprise a separate population of cells. Electrophysiological collision experiments were also performed, with stimulating electrodes in the two brachia of the superior colliculi and a recording electrode in one optic nerve. A collision effect was not detected, thus supporting the anatomical findings of rare bilateral branching of optic nerve axons. The occurrence of BPRGCs may reflect occasional ambiguities in the cues that guide axons through the chiasm.

  20. Arundic acid attenuates retinal ganglion cell death by increasing glutamate/aspartate transporter expression in a model of normal tension glaucoma

    PubMed Central

    Yanagisawa, M; Aida, T; Takeda, T; Namekata, K; Harada, T; Shinagawa, R; Tanaka, K

    2015-01-01

    Glaucoma is the second leading cause of blindness worldwide and is characterized by gradual visual impairment owing to progressive loss of retinal ganglion cells (RGCs) and their axons. Glutamate excitotoxicity has been implicated as a mechanism of RGC death in glaucoma. Consistent with this claim, we previously reported that glutamate/aspartate transporter (GLAST)-deficient mice show optic nerve degeneration that is similar to that observed in glaucoma. Therefore, drugs that upregulate GLAST may be useful for neuroprotection in glaucoma. Although many compounds are known to increase the expression of another glial glutamate transporter, EAAT2/GLT1, few compounds are shown to increase GLAST expression. Arundic acid is a glial modulating agent that ameliorates delayed ischemic brain damage by attenuating increases in extracellular glutamate. We hypothesized that arundic acid neuroprotection involves upregulation of GLAST. To test this hypothesis, we examined the effect of arundic acid on GLAST expression and glutamate uptake. We found that arundic acid induces GLAST expression in vitro and in vivo. In addition, arundic acid treatment prevented RGC death by upregulating GLAST in heterozygous (GLAST+/−) mice. Furthermore, arundic acid stimulates the human GLAST ortholog, EAAT1, expression in human neuroglioblastoma cells. Thus, discovering compounds that can enhance EAAT1 expression and activity may be a novel strategy for therapeutic treatment of glaucoma. PMID:25789968

  1. Caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury is mediated via RhoA and ROCK activation in major pelvic ganglion

    PubMed Central

    Hannan, Johanna L.; Matsui, Hotaka; Sopko, Nikolai A.; Liu, Xiaopu; Weyne, Emmanuel; Albersen, Maarten; Watson, Joseph W.; Hoke, Ahmet; Burnett, Arthur L.; Bivalacqua, Trinity J.

    2016-01-01

    Axonal injury due to prostatectomy leads to Wallerian degeneration of the cavernous nerve (CN) and erectile dysfunction (ED). Return of potency is dependent on axonal regeneration and reinnervation of the penis. Following CN injury (CNI), RhoA and Rho-associated protein kinase (ROCK) increase in penile endothelial and smooth muscle cells. Previous studies indicate that nerve regeneration is hampered by activation of RhoA/ROCK pathway. We evaluated the role of RhoA/ROCK pathway in CN regulation following CNI using a validated rat model. CNI upregulated gene and protein expression of RhoA/ROCK and caspase-3 mediated apoptosis in the major pelvic ganglion (MPG). ROCK inhibitor (ROCK-I) prevented upregulation of RhoA/ROCK pathway as well as activation of caspase-3 in the MPG. Following CNI, there was decrease in the dimer to monomer ratio of neuronal nitric oxide synthase (nNOS) protein and lowered NOS activity in the MPG, which were prevented by ROCK-I. CNI lowered intracavernous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent with ED. ROCK-I maintained the intracavernous pressure and non-adrenergic non-cholinergic-mediated relaxation in the penis following CNI. These results suggest that activation of RhoA/ROCK pathway mediates caspase-3 dependent apoptosis of nitrergic neurons in the MPG following CNI and that ROCK-I can prevent post-prostatectomy ED. PMID:27388816

  2. Caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury is mediated via RhoA and ROCK activation in major pelvic ganglion.

    PubMed

    Hannan, Johanna L; Matsui, Hotaka; Sopko, Nikolai A; Liu, Xiaopu; Weyne, Emmanuel; Albersen, Maarten; Watson, Joseph W; Hoke, Ahmet; Burnett, Arthur L; Bivalacqua, Trinity J

    2016-01-01

    Axonal injury due to prostatectomy leads to Wallerian degeneration of the cavernous nerve (CN) and erectile dysfunction (ED). Return of potency is dependent on axonal regeneration and reinnervation of the penis. Following CN injury (CNI), RhoA and Rho-associated protein kinase (ROCK) increase in penile endothelial and smooth muscle cells. Previous studies indicate that nerve regeneration is hampered by activation of RhoA/ROCK pathway. We evaluated the role of RhoA/ROCK pathway in CN regulation following CNI using a validated rat model. CNI upregulated gene and protein expression of RhoA/ROCK and caspase-3 mediated apoptosis in the major pelvic ganglion (MPG). ROCK inhibitor (ROCK-I) prevented upregulation of RhoA/ROCK pathway as well as activation of caspase-3 in the MPG. Following CNI, there was decrease in the dimer to monomer ratio of neuronal nitric oxide synthase (nNOS) protein and lowered NOS activity in the MPG, which were prevented by ROCK-I. CNI lowered intracavernous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent with ED. ROCK-I maintained the intracavernous pressure and non-adrenergic non-cholinergic-mediated relaxation in the penis following CNI. These results suggest that activation of RhoA/ROCK pathway mediates caspase-3 dependent apoptosis of nitrergic neurons in the MPG following CNI and that ROCK-I can prevent post-prostatectomy ED.

  3. Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

    NASA Astrophysics Data System (ADS)

    Jensen, Ralph J.; Rizzo, Joseph F., III

    2011-06-01

    An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

  4. Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress

    PubMed Central

    Sappington, Rebecca M; Sidorova, Tatiana; Ward, Nicholas J; Chakravarthy, Rohini; Ho, Karen W; Calkins, David J

    2015-01-01

    Our recent studies implicate the transient receptor potential vanilloid-1 (TRPV1) channel as a mediator of retinal ganglion cell (RGC) function and survival. With elevated pressure in the eye, TRPV1 increases in RGCs, supporting enhanced excitability, while Trpv1 -/- accelerates RGC degeneration in mice. Here we find TRPV1 localized in monkey and human RGCs, similar to rodents. Expression increases in RGCs exposed to acute changes in pressure. In retinal explants, contrary to our animal studies, both Trpv1 -/- and pharmacological antagonism of the channel prevented pressure-induced RGC apoptosis, as did chelation of extracellular Ca2+. Finally, while TRPV1 and TRPV4 co-localize in some RGC bodies and form a protein complex in the retina, expression of their mRNA is inversely related with increasing ocular pressure. We propose that TRPV1 activation by pressure-related insult in the eye initiates changes in expression that contribute to a Ca2+-dependent adaptive response to maintain excitatory signaling in RGCs. PMID:25713995

  5. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Muscular inflammation, degeneration... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found... carcass shall be condemned. (b) If muscular lesions are found to be distributed in such a manner or to...

  6. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. PMID:26572116

  7. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index.

  8. Does lumbar facet arthrosis precede disc degeneration? A postmortem study.

    PubMed

    Eubanks, Jason David; Lee, Michael J; Cassinelli, Ezequiel; Ahn, Nicholas U

    2007-11-01

    It is believed lumbar degeneration begins in the disc, where desiccation and collapse lead to instability and compensatory facet arthrosis. We explored the contrary contention that facet degeneration precedes disc degeneration by examining 647 skeletal lumbar spines. Using facet osteophytosis as a measure of facet degeneration and vertebral rim osteophytosis as a measure of disc degeneration, we assumed bone degeneration in both locations equally reflected the progression of those in the soft tissues. We graded arthrosis Grade 0 to 4 on a continuum from no arthritis to ankylosis. The data were analyzed for different age groups to examine patterns of degeneration with age. Specimens younger than 30 years of age had a higher prevalence of facet osteophytosis compared with vertebral rim osteophotosis at L1-L2 and L2-L3. Specimens aged 30 to 39 years showed more facet osteophytosis than vertebral rim osteophytosis at L4-L5. Specimens older than 40 years, however, showed more vertebral rim osteophytosis compared with facet osteophytosis at all levels except L4-L5 and L5-S1. This skeletal study suggests facet osteophytosis appears early in the degenerative process, preceding vertebral rim osteophytosis of degenerating intervertebral discs. However, once facets begin deteriorating with age, vertebral rim osteophytosis overtakes continued facet osteophytosis. These data challenge the belief that facet osteophytosis follows vertebral rim osteophytosis; rather, it appears vertebral rim osteophytosis progresses more rapidly in later years, but facet osteophotosis occurs early, predominating in younger individuals.

  9. Retinas in a Dish Peek into Inherited Retinal Degeneration.

    PubMed

    Duong, Thu T; Vasireddy, Vidyullatha; Mills, Jason A; Bennett, Jean

    2016-06-01

    Human retinal degeneration can cause blindness, and the lack of relevant model systems has made identifying underlying mechanisms challenging. Parfitt et al. (2016) generate three-dimensional retinal tissue from patient-derived induced pluripotent stem cells to identify how CEP290 mutations cause retinal degeneration, and show an antisense approach can correct disease-associated phenotypes. PMID:27257755

  10. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    SciTech Connect

    Abbas, G. Sarfraz, M.; Shah, H. A.

    2014-09-15

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

  11. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    NASA Astrophysics Data System (ADS)

    Abbas, G.; Sarfraz, M.; Shah, H. A.

    2014-09-01

    Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

  12. Elevation of intracellular calcium levels in spiral ganglion cells by trimethyltin.

    PubMed

    Fechter, L D; Liu, Y

    1995-11-01

    The neurotoxicant, trimethyltin (TMT) produces cochlear impairment at far lower dose levels and far more rapidly than it does central nervous system effects. The initial effects of TMT in the cochlea, in vivo, are consistent with disruption of the inner hair cell type-1 spiral ganglion cell synapse although it is uncertain whether the effect is on presynaptic and/or postsynaptic units. This synapse is believed to be an excitatory glutamatergic one, providing the possibility that TMT could induce an excitotoxic process resulting in elevations in intracellular calcium ([Ca2+]i). The objective of this study was to determine whether TMT had direct toxic effects on the postsynaptic spiral ganglion cells studied in primary culture and to identify the role of extracellular calcium in such an effect. The marker of interest was the effect of this agent on [Ca2+]i levels as determined using quantitation of the fluorescent calcium dye, Fura-2. TMT did induce a marked and sustained elevation in [Ca2+]i level in the spiral ganglion cells that appeared to have a rapid initial phase and a slower saturating phase. Studies performed using calcium-free medium showed that elevation of [Ca2+]i in spiral ganglion cells by TMT was attenuated but not entirely blocked. Further, the L-type calcium channel blocker, nifedipine, was able to inhibit the initial increase in [Ca2+]i, suggesting that at least this phase of the TMT effect was mediated by calcium channels, although nifedipine had no significant effect on the time to reach the maximal [Ca2+]i level. Parallel control experiments performed using application of exogenous glutamate and depolarizing K+ concentrations also produced elevation in [Ca2+]i levels. The data indicate that TMT elevates [Ca2+]i in isolated spiral ganglion cells both by increasing extracellular uptake via Ca2+ channels and also by releasing Ca2+ from intracellular stores. Thus TMT ototoxicity appears to include a direct postsynaptic toxic event. PMID:8647712

  13. Homocysteine-Mediated Modulation of Mitochondrial Dynamics in Retinal Ganglion Cells

    PubMed Central

    Ganapathy, Preethi S.; Perry, Richard L.; Tawfik, Amany; Smith, Robert M.; Perry, Elizabeth; Roon, Penny; Bozard, B. Renee; Ha, Yonju

    2011-01-01

    Purpose. To evaluate the effect of excess homocysteine on the regulation of retinal ganglion cell mitochondrial dynamics. Methods. Mice deficient in cystathionine-β-synthase (cbs) were used as a model of hyperhomocysteinemia. Gene and protein expression analyses of Opa1 and Fis1 were performed on cbs+/−neural retinas. Mitochondria within retinal ganglion cell axons underwent systematic ultrastructural analysis to measure area, length, width, and the distance between the mitochondria and the axon wall. Primary mouse ganglion cells were cultured, treated with homocysteine, and assessed for levels of Opa1 and Fis1 protein, the number of mitochondria per length of neurite, and levels of cleaved caspase-3. Results. Opa1 and Fis1 protein levels in cbs+/− neural retinas were elevated to 191.00% ± 26.40% and 226.20% ± 4.57%, respectively, compared with wild-type. Mitochondria of cbs+/− retinas were smaller in all parameters studied, including area (0.32 ± 0.01μm2 vs. 0.42 ± 0.02 μm2), compared with wild-type. Primary ganglion cells treated with homocysteine had elevations in Opa1 and Fis1 proteins, a significantly higher number of mitochondria per length of neurite (0.1781 ± 0.017 vs. 0.1156 ± 0.012), and significantly higher levels of cleaved caspase-3 compared with control. Conclusions. This study provides the first evidence that homocysteine-induced ganglion cell loss involves the dysregulation of mitochondrial dynamics, both in vivo and in vitro. The present data suggest increased mitochondrial fission as a novel mechanism of homocysteine toxicity to neurons. Of particular relevance are glaucoma and Alzheimer's disease, neurodegenerative diseases that are associated with hyperhomocysteinemia and, more recently, have implicated increased mitochondrial fission in their pathogeneses. PMID:21642619

  14. Reactive oxygen species alters the electrophysiological properties and raises [Ca2+]i in intracardiac ganglion neurons.

    PubMed

    Dyavanapalli, Jhansi; Rimmer, Katrina; Harper, Alexander A

    2010-07-01

    We have investigated the effects of the reactive oxygen species (ROS) donors hydrogen peroxide (H(2)O(2)) and tert-butyl hydroperoxide (t-BHP) on the intrinsic electrophysiological characteristics: ganglionic transmission and resting [Ca(2+)](i) in neonate and adult rat intracardiac ganglion (ICG) neurons. Intracellular recordings were made using sharp microelectrodes filled with either 0.5 M KCl or Oregon Green 488 BAPTA-1, allowing recording of electrical properties and measurement of [Ca(2+)](i). H(2)O(2) and t-BHP both hyperpolarized the resting membrane potential and reduced membrane resistance. In adult ICG neurons, the hyperpolarizing action of H(2)O(2) was reversed fully by Ba(2+) and partially by tetraethylammonium, muscarine, and linopirdine. H(2)O(2) and t-BHP reduced the action potential afterhyperpolarization (AHP) amplitude but had no impact on either overshoot or AHP duration. ROS donors evoked an increase in discharge adaptation to long depolarizing current pulses. H(2)O(2) blocked ganglionic transmission in most ICG neurons but did not alter nicotine-evoked depolarizations. By contrast, t-BHP had no significant action on ganglionic transmission. H(2)O(2) and t-BHP increased resting intracellular Ca(2+) levels to 1.6 ( +/- 0.6, n = 11, P < 0.01) and 1.6 ( +/- 0.3, n = 8, P < 0.001), respectively, of control value (1.0, approximately 60 nM). The ROS scavenger catalase prevented the actions of H(2)O(2), and this protection extended beyond the period of application. Superoxide dismutase partially shielded against the action of H(2)O(2), but this was limited to the period of application. These data demonstrate that ROS decreases the excitability and ganglionic transmission of ICG neurons, attenuating parasympathetic control of the heart. PMID:20445155

  15. Inhibition of Adult Rat Retinal Ganglion Cells by D1-type Dopamine Receptor Activation

    PubMed Central

    Hayashida, Yuki; Rodríguez, Carolina Varela; Ogata, Genki; Partida, Gloria J.; Oi, Hanako; Stradleigh, Tyler W.; Lee, Sherwin C.; Colado, Anselmo Felipe; Ishida, Andrew T.

    2011-01-01

    The spike output of neural pathways can be regulated by modulating output neuron excitability and/or their synaptic inputs. Dopaminergic interneurons synapse onto cells that route signals to mammalian retinal ganglion cells, but it is unknown whether dopamine can activate receptors in these ganglion cells and, if it does, how this affects their excitability. Here, we show D1a-receptor-like immunoreactivity in ganglion cells identified in adult rats by retrogradely transported dextran, and that dopamine, D1-type receptor agonists, and cAMP analogs inhibit spiking in ganglion cells dissociated from adult rats. These ligands curtailed repetitive spiking during constant current injections, and reduced the number and rate of rise of spikes elicited by fluctuating current injections without significantly altering the timing of the remaining spikes. Consistent with mediation by D1-type receptors, SCH-23390 reversed the effects of dopamine on spikes. Contrary to a recent report, spike inhibition by dopamine was not precluded by blocking Ih. Consistent with the reduced rate of spike rise, dopamine reduced voltage-gated Na+ current (INa) amplitude and tetrodotoxin, at doses that reduced INa as moderately as dopamine, also inhibited spiking. These results provide the first direct evidence that D1-type dopamine receptor activation can alter mammalian retinal ganglion cell excitability, and demonstrate that dopamine can modulate spikes in these cells by a mechanism different from the pre- and postsynaptic means proposed by previous studies. To our knowledge, our results also provide the first evidence that dopamine receptor activation can reduce excitability without altering the temporal precision of spike firing. PMID:19940196

  16. Diffuse Bipolar Cells Provide Input to OFF Parasol Ganglion Cells in the Macaque Retina

    PubMed Central

    JACOBY, ROY A.; WIECHMANN, ALLAN F.; AMARA, SUSAN G.; LEIGHTON, BARBARA H.; MARSHAK, DAVID W.

    2012-01-01

    Parasol retinal ganglion cells are more sensitive to luminance contrast and respond more transiently at all levels of adaptation than midget ganglion cells. This may be due, in part, to differences between bipolar cells that provide their input, and the goal of these experiments was to study these differences. Midget bipolar cells are known to be presynaptic to midget ganglion cells. To identify the bipolar cells presynaptic to parasol cells, these ganglion cells were intracellularly injected with Neurobiotin, cone bipolar cells were immunolabeled, and the double-labeled material was analyzed. In the electron microscope, we found that DB3 diffuse bipolar cells labeled by using antiserum to calbindin D-28k were presynaptic to OFF parasol cells. In the confocal microscope, DB3 bipolars costratified with OFF parasol cell dendrites and made significantly more appositions with them than expected due to chance. Flat midget bipolar cells were labeled with antiserum to recoverin. Although they made a few appositions with parasol cells, the number was no greater than would be expected when two sets of processes have overlapping distributions in the inner plexiform layer. DB2 diffuse bipolar cells were labeled with antibodies to excitatory amino acid transporter 2, and they also made appositions with OFF parasol cells. These results suggest that DB2 bipolar cells are also presynaptic to OFF parasol ganglion cells, but midget bipolar cells are not. We estimate that midperipheral OFF parasol cells receive ≈500 synapses from 50 DB3 bipolar cells that, in turn, receive input from 250 cones. PMID:10578099

  17. Classification of retinal ganglion cells in the southern hemisphere lamprey Geotria australis (Cyclostomata).

    PubMed

    Fletcher, Lee Norman; Coimbra, João Paulo; Rodger, Jennifer; Potter, Ian C; Gill, Howard S; Dunlop, Sarah A; Collin, Shaun P

    2014-03-01

    Lampreys are one of two extant representatives of the earliest group of vertebrates, the agnathans or jawless fishes. The single species of the southern hemisphere lamprey family Geotriidae, Geotria australis, possesses the potential for pentachromatic color discrimination opposed to the mono- or dichromacy found in other lampreys. However, little is known of the retinal ganglion cell types that contribute to visual processing in G. australis. A quantitative morphological approach was used to distinguish and describe retinal ganglion cell types in G. australis. The morphology of retinal ganglion cells was revealed by retrograde biocytin labeling from the optic disc. Cells were digitally reconstructed, and somatic area and position and dendritic field size, density, tortuosity, and stratification were subjected to quantitative morphometric analyses. Cluster analysis, in conjunction with similarity profile analysis (SIMPROF), statistically identified five discrete monostratified retinal ganglion cell types, one of which may comprise two subtypes. Two bistratified types were identified separately, including a biplexiform and a bistratified subtype. The use of cluster analysis with SIMPROF provided a robust statistical technique for objectively identifying cell types whose characteristics were similar and significantly different from those of other types and thus provides an objective resolution of the problems posed by "lumpers vs. splitters" when designating cell types. The diversity of retinal ganglion cells suggests that visual information in the lamprey G. australis is processed in parallel streams, as in gnathostomes. These findings, together with the results of previous studies, indicate that the visual system of the lamprey G. australis represents the upper limit of visual complexity in extant agnathans.

  18. Identification of AⅡ amacrine, displaced amacrine, and bistratified ganglion cell types in human retina with antibodies against calretinin.

    PubMed

    Lee, Sammy C S; Weltzien, Felix; Madigan, Michele C; Martin, Paul R; Grünert, Ulrike

    2016-01-01

    Antibodies against calretinin are markers for one type of rod pathway interneuron (AⅡ amacrine cell) in the retina of some but not all mammalian species. The AⅡ cells play a crucial role in night-time (scotopic) vision and have been proposed as a target for optogenetic restoration of vision in retinal disease. In the present study we aimed to characterize the AⅡ cells in human retina. Postmortem human donor eyes were obtained with ethical approval and processed for calretinin immunofluorescence. Calretinin-positive somas in the inner nuclear and the ganglion cell layer were filled with the lipophilic dye DiI. The large majority (over 80%) of calretinin-immunoreactive cells is located in the inner nuclear layer, is immunopositive for glycine transporter 1, and shows the typical morphology of AⅡ amacrine cells. In addition, a small proportion of calretinin-positive cells in the inner nuclear layer and in the ganglion cell layer is glutamic acid decarboxylase-positive and shows the morphology of widefield amacrine cells (stellate, semilunar, and thorny amacrine cells). About half of the calretinin cells in the ganglion cell layer are bistratified ganglion cells resembling the small bistratified (presumed blue-ON/yellow-OFF) and the G17 ganglion cell previously described in primates. We conclude that in human retina, antibodies against calretinin can be used to identify AⅡ amacrine cells in the inner nuclear layer as well as widefield amacrine and small bistratified ganglion cells in the ganglion cell layer. PMID:26053777

  19. Non-Invasive Detection of Early Retinal Neuronal Degeneration by Ultrahigh Resolution Optical Coherence Tomography

    PubMed Central

    Tudor, Debbie; Kajić, Vedran; Rey, Sara; Erchova, Irina; Považay, Boris; Hofer, Bernd; Powell, Kate A.; Marshall, David; Rosin, Paul L.; Drexler, Wolfgang; Morgan, James E.

    2014-01-01

    Optical coherence tomography (OCT) has revolutionises the diagnosis of retinal disease based on the detection of microscopic rather than subcellular changes in retinal anatomy. However, currently the technique is limited to the detection of microscopic rather than subcellular changes in retinal anatomy. However, coherence based imaging is extremely sensitive to both changes in optical contrast and cellular events at the micrometer scale, and can generate subtle changes in the spectral content of the OCT image. Here we test the hypothesis that OCT image speckle (image texture) contains information regarding otherwise unresolvable features such as organelle changes arising in the early stages of neuronal degeneration. Using ultrahigh resolution (UHR) OCT imaging at 800 nm (spectral width 140 nm) we developed a robust method of OCT image analyses, based on spatial wavelet and texture-based parameterisation of the image speckle pattern. For the first time we show that this approach allows the non-invasive detection and quantification of early apoptotic changes in neurons within 30 min of neuronal trauma sufficient to result in apoptosis. We show a positive correlation between immunofluorescent labelling of mitochondria (a potential source of changes in cellular optical contrast) with changes in the texture of the OCT images of cultured neurons. Moreover, similar changes in optical contrast were also seen in the retinal ganglion cell- inner plexiform layer in retinal explants following optic nerve transection. The optical clarity of the explants was maintained throughout in the absence of histologically detectable change. Our data suggest that UHR OCT can be used for the non-invasive quantitative assessment of neuronal health, with a particular application to the assessment of early retinal disease. PMID:24776961

  20. Noise-Induced Neural Degeneration and Therapeutic Effect of Antioxidant Drugs

    PubMed Central

    Choi, Seong Hee

    2015-01-01

    The primary site of lesion induced by noise exposure is the hair cells in the organ of Corti and the primary neural degeneration occurs in synaptic terminals of cochlear nerve fibers and spiral ganglion cells. The cellular basis of noise-induced hearing loss is oxidative stress, which refers to a severe disruption in the balance between the production of free radicals and antioxidant defense system in the cochlea by excessive production of free radicals induced by noise exposure. Oxidative stress has been identified by a variety of biomarkers to label free radical activity which include four-hydroxy-2-nonenal, nitrotyrosine, and malondialdehyde, and inducible nitric oxide synthase, cytochrome-C, and cascade-3, 8, 9. Furthermore, oxidative stress is contributing to the necrotic and apoptotic cell deaths in the cochlea. To counteract the known mechanisms of pathogenesis and oxidative stress induced by noise exposure, a variety of antioxidant drugs including oxygen-based antioxidants such as N-acetyl-L-cystein and acetyl-L-carnitine and nitrone-based antioxidants such as phenyl-N-tert-butylnitrone (PBN), disufenton sodium, 4-hydroxy PBN, and 2, 4-disulfonyl PBN have been used in our laboratory. These antioxidant drugs were effective in preventing or treating noise-induced hearing loss. In combination with other antioxidants, antioxidant drugs showed a strong synergistic effect. Furthermore, successful use of antioxidant drugs depends on the optimal timing of treatment and the duration of treatment, which are highly related to the time window of free radical formation induced by noise exposure. PMID:26771008

  1. Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies.

    PubMed

    Carelli, Valerio; Ross-Cisneros, Fred N; Sadun, Alfredo A

    2002-05-01

    Selective degeneration of the smallest fibers (papillo-macular bundle) of the human optic nerve occurs in a large number of optic neuropathies characterized primarily by loss of central vision. The pathophysiology that underlies this peculiar pattern of cell involvement probably reflects different forms of genetic and acquired mitochondrial dysfunction. Maternally inherited Leber's hereditary optic neuropathy (LHON), dominant optic atrophy (Kjer disease), the optic atrophy of Leigh's syndrome, Friedreich ataxia and a variety of other conditions are examples of inherited mitochondrial disorders with different etiologies. Tobacco-alcohol amblyopia (TAA), the Cuban epidemic of optic neuropathy (CEON) and other dietary (Vitamins B, folate deficiencies) optic neuropathies, as well as toxic optic neuropathies such as due to chloramphenicol, ethambutol, or more rarely to carbon monoxide, methanol and cyanide are probably all related forms of acquired mitochondrial dysfunction. Biochemical and cellular studies in LHON point to a partial defect of respiratory chain function that may generate either an ATP synthesis defect and/or a chronic increase of oxidative stress. Histopathological studies in LHON cases and a rat model mimicking CEON revealed a selective loss of retinal ganglion cells (RGCs) and the corresponding axons, particularly in the temporal-central part of the optic nerve. Anatomical peculiarities of optic nerve axons, such as the asymmetric pattern of myelination, may have functional implications on energy dependence and distribution of mitochondrial populations in the different sections of the nerve. Histological evidence suggests impaired axonal transport of mitochondria in LHON and in the CEON-like rat model, indicating a possible common pathophysiology for this category of optic neuropathies. Histological evidence of myelin pathology in LHON also suggests a role for oxidative stress, possibly affecting the oligodendrocytes of the optic nerves.

  2. Rpe65 as a modifier gene for inherited retinal degeneration

    PubMed Central

    Samardzija, M.; Wenzel, A.; Naash, M.; Remé, C. E.; Grimm, C.

    2009-01-01

    Light accelerates progression of retinal degeneration in many animal models of retinitis pigmentosa (RP). A sequence variant in the Rpe65 gene (Rpe65450Leu or Rpe65450Met) can act as a modulator of light-damage susceptibility in mice by influencing the kinetics of rhodopsin regeneration and thus by modulating the photon absorption. Depending on exposure duration and light intensity applied, white fluorescent light induces photoreceptor apoptosis and retinal degeneration in wild-type mice by the activation of one of two known molecular pathways. These pathways depend, respectively, on activation of the transcription factor c-Fos/AP-1 and on phototransduction activity. Here we tested Rpe65 as a genetic modifier for inherited retinal degeneration and analysed which degenerative pathway is activated in a transgenic mouse model of autosomal dominant RP. We show that retinal degeneration was reduced in mice expressing the Rpe65450Met variant and that these mice retained more visual pigment rhodopsin than did transgenic mice expressing the Rpe65450Leu variant. In addition, lack of phototransduction slowed retinal degeneration whereas ablation of c-Fos had no effect. We conclude that sequence variations in the Rpe65 gene can act as genetic modifiers in inherited retinal degeneration, presumably by regulating the daily rate of photon absorption through the modulation of rhodopsin regeneration kinetics. Increased absorption of photons and/or light sensitivity appear to accelerate retinal degeneration via an apoptotic cascade which involves phototransduction but not c-Fos. PMID:16519667

  3. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  4. Disruption in dopaminergic innervation during photoreceptor degeneration.

    PubMed

    Ivanova, Elena; Yee, Christopher W; Sagdullaev, Botir T

    2016-04-15

    Dopaminergic amacrine cells (DACs) release dopamine in response to light-driven synaptic inputs, and are critical to retinal light adaptation. Retinal degeneration (RD) compromises the light responsiveness of the retina and, subsequently, dopamine metabolism is impaired. As RD progresses, retinal neurons exhibit aberrant activity, driven by AII amacrine cells, a primary target of the retinal dopaminergic network. Surprisingly, DACs are an exception to this physiological change; DACs exhibit rhythmic activity in healthy retina, but do not burst in RD. The underlying mechanism of this divergent behavior is not known. It is also unclear whether RD leads to structural changes in DACs, impairing functional regulation of AII amacrine cells. Here we examine the anatomical details of DACs in three mouse models of human RD to determine how changes to the dopaminergic network may underlie physiological changes in RD. By using rd10, rd1, and rd1/C57 mice we were able to dissect the impacts of genetic background and the degenerative process on DAC structure in RD retina. We found that DACs density, soma size, and primary dendrite length are all significantly reduced. Using a novel adeno-associated virus-mediated technique to label AII amacrine cells in mouse retina, we observed diminished dopaminergic contacts to AII amacrine cells in RD mice. This was accompanied by changes to the components responsible for dopamine synthesis and release. Together, these data suggest that structural alterations of the retinal dopaminergic network underlie physiological changes during RD.

  5. Genetic Factors in Intervertebral Disc Degeneration

    PubMed Central

    Feng, Yi; Egan, Brian; Wang, Jinxi

    2016-01-01

    Low back pain (LBP) is a major cause of disability and imposes huge economic burdens on human society worldwide. Among many factors responsible for LBP, intervertebral disc degeneration (IDD) is the most common disorder and is a target for intervention. The etiology of IDD is complex and its mechanism is still not completely understood. Many factors such as aging, spine deformities and diseases, spine injuries, and genetic factors are involved in the pathogenesis of IDD. In this review, we will focus on the recent advances in studies on the most promising and extensively examined genetic factors associated with IDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc’s mechanical properties and metabolic activities. These genetic and proteomic studies have begun to shed light on the molecular basis of IDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of IDD, specific early diagnosis and more effective treatments for this disabling disease will be possible in the future. PMID:27617275

  6. [Multiple system atrophy - synuclein and neuronal degeneration].

    PubMed

    Yoshida, Mari

    2011-11-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmarks are α-synuclein (AS) positive glial cytoplasmic inclusions (GCIs) in oligodendroglias. AS aggregation is also found in glial nuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurties. Reviewing the pathological features of 102 MSA cases, OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases, which suggested different phenotypic pattern of MSA might exist between races, compared to the relatively high frequency of SND-type in western countries. In early stage of MSA, NNIs, NCIs and diffuse homogenous stain of AS in neuronal nuclei and cytoplasm were observed in various vulnerable lesions including the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of thoracic cord, lower motor neurons and cortical pyramidal neurons, in additions to GCIs. These findings indicated that the primary nonfibrillar and fibrillar AS aggregation also occurred in neurons. Therefore both the direct involvement of neurons themselves and the oligodendroglia-myelin-axon mechanism may synergistically accelerate the degenerative process of MSA. PMID:22277386

  7. CERKL Knockdown Causes Retinal Degeneration in Zebrafish

    PubMed Central

    Riera, Marina; Burguera, Demian; Garcia-Fernàndez, Jordi; Gonzàlez-Duarte, Roser

    2013-01-01

    The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration. PMID:23671706

  8. Widespread cytoskeletal pathology characterizes corticobasal degeneration.

    PubMed Central

    Feany, M. B.; Dickson, D. W.

    1995-01-01

    Corticobasal degeneration (CBD) is a rare, progressive neurological disorder characterized by widespread neuronal and glial pathology. Using immunohistochemistry and laser confocal microscopy, we demonstrate that the nonamyloid cortical plaques of CBD are actually collections of abnormal tau in the distal processes of astrocytes. These glial cells express both vimentin and CD44, markers of astrocyte activation. Glial pathology also includes tau-positive cytoplasmic inclusions, here localized to Leu 7-expressing oligodendrocytes. In addition, a wide array of neuronal pathology is defined with tau-positive inclusions in multiple domains of a variety of cortical neurons. CBD thus exhibits widespread glial and neuronal cytoskeletal pathology, including a novel structure, the astrocytic plaque. CBD is a disease of generalized cytoskeletal disruption affecting several cell types and multiple domains of these cells. The further definition of CBD pathology refines the diagnosis and pathophysiological understanding of this unique disease and has important implications for other neurodegenerative diseases, like Alzheimer's disease, characterized by abnormal tau deposition. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778678

  9. Evidence for degenerate tetraploidy in bdelloid rotifers.

    PubMed

    Mark Welch, David B; Mark Welch, Jessica L; Meselson, Matthew

    2008-04-01

    Rotifers of class Bdelloidea have evolved for millions of years apparently without sexual reproduction. We have sequenced 45- to 70-kb regions surrounding the four copies of the hsp82 gene of the bdelloid rotifer Philodina roseola, each of which is on a separate chromosome. The four regions comprise two colinear gene-rich pairs with gene content, order, and orientation conserved within each pair. Only a minority of genes are common to both pairs, also in the same orientation and order, but separated by gene-rich segments present in only one or the other pair. The pattern is consistent with degenerate tetraploidy with numerous segmental deletions, some in one pair of colinear chromosomes and some in the other. Divergence in 1,000-bp windows varies along an alignment of a colinear pair, from zero to as much as 20% in a pattern consistent with gene conversion associated with recombinational repair of DNA double-strand breaks. Although pairs of colinear chromosomes are a characteristic of sexually reproducing diploids and polyploids, a quite different explanation for their presence in bdelloids is suggested by the recent finding that bdelloid rotifers can recover and resume reproduction after suffering hundreds of radiation-induced DNA double-strand breaks per oocyte nucleus. Because bdelloid primary oocytes are in G(1) and therefore lack sister chromatids, we propose that bdelloid colinear chromosome pairs are maintained as templates for the repair of DNA double-strand breaks caused by the frequent desiccation and rehydration characteristic of bdelloid habitats.

  10. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  11. Chronic nerve root entrapment: compression and degeneration

    NASA Astrophysics Data System (ADS)

    Vanhoestenberghe, A.

    2013-02-01

    Electrode mounts are being developed to improve electrical stimulation and recording. Some are tight-fitting, or even re-shape the nervous structure they interact with, for a more selective, fascicular, access. If these are to be successfully used chronically with human nerve roots, we need to know more about the possible damage caused by the long-term entrapment and possible compression of the roots following electrode implantation. As there are, to date, no such data published, this paper presents a review of the relevant literature on alternative causes of nerve root compression, and a discussion of the degeneration mechanisms observed. A chronic compression below 40 mmHg would not compromise the functionality of the root as far as electrical stimulation and recording applications are concerned. Additionally, any temporary increase in pressure, due for example to post-operative swelling, should be limited to 20 mmHg below the patient’s mean arterial pressure, with a maximum of 100 mmHg. Connective tissue growth may cause a slower, but sustained, pressure increase. Therefore, mounts large enough to accommodate the root initially without compressing it, or compliant, elastic, mounts, that may stretch to free a larger cross-sectional area in the weeks after implantation, are recommended.

  12. Mechanisms of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Fowler, Benjamin J.

    2012-01-01

    Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed. PMID:22794258

  13. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  14. The genetics of frontotemporal lobar degeneration.

    PubMed

    Rademakers, Rosa; Hutton, Mike

    2007-09-01

    The clinical disorders associated with frontotemporal lobar degeneration (FTLD) are increasingly recognized as an important cause of early-onset dementia. Patients usually present with progressive changes in personality, behavior, or language, progressing to general cognitive impairment and ultimately death. In the past decade, improved clinical and histopathologic characterization uncovered extensive heterogeneity, and multiple clinical and pathologic FTLD subtypes were defined. Simultaneously, the discovery of four causal FTLD genes emphasized the genetic complexity associated with FTLD. More recently, the field of FTLD has gained increased attention as a result of two major findings. First, mutations in the progranulin gene (PGRN) were recognized as a major cause of FTLD with ubiquitin-positive and tau-negative inclusions (FTLD-U), and subsequently the TAR DNA-binding protein-43 (TDP-43) was identified as a key protein within the ubiquitinated inclusions in FTLD-U and amyotrophic lateral sclerosis (ALS). In this report, we outline the progress made in the study of the genetic etiologies and neuropathologic substrates in FTLD.

  15. Lithium Alters the Morphology of Neurites Regenerating from Cultured Adult Spiral Ganglion Neurons

    PubMed Central

    Shah, S. M.; Patel, C. H.; Feng, A. S.; Kollmar, R.

    2013-01-01

    The small-molecule drug lithium (as a monovalent ion) promotes neurite regeneration and functional recovery, is easy to administer, and is approved for human use to treat bipolar disorder. Lithium exerts its neuritogenic effect mainly by inhibiting glycogen synthase kinase 3, a constitutively-active serine/threonine kinase that is regulated by neurotrophin and “wingless-related MMTV integration site” (Wnt) signaling. In spiral ganglion neurons of the cochlea, the effects of lithium and the function of glycogen synthase kinase 3 have not been investigated. We, therefore, set out to test whether lithium modulates neuritogenesis from adult spiral ganglion neurons. Primary cultures of dissociated spiral ganglion neurons from adult mice were exposed to lithium at concentrations between 0 and 12.5 mM. The resulting neurite morphology and growth-cone appearance were measured in detail by using immunofluorescence microscopy and image analysis. We found that lithium altered the morphology of regenerating neurites and their growth cones in a differential, concentration-dependent fashion. Low concentrations of 0.5 to 2.5 mM (around the half-maximal inhibitory concentration for glycogen synthase kinase 3 and the recommended therapeutic serum concentration for bipolar disorder) enhanced neurite sprouting and branching. A high concentration of 12.5 mM, in contrast, slowed elongation. As the lithium concentration rose from low to high, the microtubules became increasingly disarranged and the growth cones more arborized. Our results demonstrate that lithium selectively stimulates phases of neuritogenesis that are driven by microtubule reorganization. In contrast, most other drugs that have previously been tested on spiral ganglion neurons are reported to inhibit neurite outgrowth or affect only elongation. Lithium sensitivity is a necessary, but not sufficient condition for the involvement of glycogen synthase kinase 3. Our results are, therefore, consistent with, but do not

  16. Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection.

    PubMed Central

    Liu, T; Tang, Q; Hendricks, R L

    1996-01-01

    Following herpes simplex virus type 1 (HSV-1) infection of the cornea, the virus is transmitted to the trigeminal ganglion, where a brief period of virus replication is followed by establishment of a latent infection in neurons. A possible role of the immune system in regulating virus replication and maintaining latency in the sensory neurons has been suggested. We have investigated the phenotype and cytokine pattern of cells that infiltrate the A/J mouse trigeminal ganglion at various times after HSV-1 corneal infection. HSV antigen expression in the trigeminal ganglion (indicative of the viral lytic cycle) increased until day 3 postinfection (p.i.) and then diminished to undetectable levels by day 7 p.i. The period of declining HSV antigen expression. was associated with a marked increase in Mac-1+ cells. These cells did not appear to coexpress the F4/80+ (macrophage) or the CD8+ (T cell) markers, and none showed polymorphonuclear leukocyte morphology, suggesting a possible early infiltration of natural killer cells. There was also a significant increase in the trigeminal ganglion of cells expressing the gamma delta T-cell receptor, and these cells were found almost exclusively in very close association with neurons. This period was also characterized by a rapid and equivalent increase in cells expressing gamma interferon and interleukin-4. The density of the inflammatory infiltrate in the trigeminal ganglion increased until days 12 to 21 p.i., when it was predominated by CD8+, Mac-1+, and tumor necrosis factor-expressing cells, which surrounded many neurons. By day 92 p.i., the inflammatory infiltrate diminished but was heaviest in mice with active periocular skin disease. Our data are consistent with the notion that gamma interferon produced by natural killer cells and/or gamma delta T cells may play an important role in limiting HSV-1 replication in the trigeminal ganglion during the acute stage of infection. In addition, tumor necrosis factor produced by CD8

  17. Degenerate and Resonant Four-Wave Mixing in Plasmas

    NASA Astrophysics Data System (ADS)

    Joshi, C.; Kitagawa, Y.; Lal, A.

    The status of degenerate and resonant four-wave mixing in plasmas is reviewed. For the degenerate case in a collisional plasma, the theory predicts and experiments demonstrate that the thermal-force contribution to the signal reflectivity dominates over the ponderomotive-force contribution. In the resonant case, the reflectivity can be enhanced over the degenerate level. Experiments show that collisions can lead to a narrow spectral width of the ion-acoustic resonance, but the effects of convection and laser heating can limit the enhancement of the reflectivity below the expected value.

  18. Local reactivity descriptors from degenerate frontier molecular orbitals

    NASA Astrophysics Data System (ADS)

    Martínez, Jorge

    2009-08-01

    Conceptual Density Functional Theory (DFT) has proposed a set of local descriptors to measure the reactivity on specific sites of a molecule, as an example dual descriptor has been successfully used in analyzing interesting systems to understand their local reactivity, however under the frozen orbital approximation (FOA), it is defined from non-degenerate frontier molecular orbitals (FMOs). In this work, the degeneration is taken into account to propose approximated expressions to obtain the dual descriptor, nucleophilic and electrophilic Fukui functions in closed-shell systems. The proposed expressions have been tested on molecules presenting degenerate FMOs.

  19. Weakly dissipative solitons in dense relativistic-degenerate plasma

    NASA Astrophysics Data System (ADS)

    Ahmad, Saeed; Ata-ur-Rahman; Khan, S. A.

    2015-07-01

    We investigate the features of weakly nonlinear waves in a collisional dense plasma consisting of ultra-relativistic degenerate electrons and non-relativistic degenerate ions. In weak dissipation limit, the dynamics of low frequency nonlinear ion (solitary) wave is described by solving a damped Korteweg-deVries equation. The analytical and numerical analysis shows the existence of weakly dissipative solitons evolving with time. The characteristics of soliton evolution with plasma number density and slow ion-neutral collision rate are discussed with some detail. The relevance of the study with degenerate plasmas in ultra-dense astrophysical objects, particularly white dwarf stars is also pointed out.

  20. Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

    PubMed Central

    Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

    2015-01-01

    Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

  1. Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a progressive retinal degeneration in mice

    PubMed Central

    Chi, Zai-Long; Akahori, Masakazu; Obazawa, Minoru; Minami, Masayoshi; Noda, Toru; Nakaya, Naoki; Tomarev, Stanislav; Kawase, Kazuhide; Yamamoto, Tetsuya; Noda, Setsuko; Sasaoka, Masaki; Shimazaki, Atsushi; Takada, Yuichiro; Iwata, Takeshi

    2010-01-01

    Glaucoma is one of the leading causes of bilateral blindness affecting nearly 8 million people worldwide. Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and is often associated with elevated intraocular pressure (IOP). However, patients with normal tension glaucoma (NTG), a subtype of primary open-angle glaucoma (POAG), develop the disease without IOP elevation. The molecular pathways leading to the pathology of NTG and POAG are still unclear. Here, we describe the phenotypic characteristics of transgenic mice overexpressing wild-type (Wt) or mutated optineurin (Optn). Mutations E50K, H486R and Optn with a deletion of the first (amino acids 153–174) or second (amino acids 426–461) leucine zipper were used for overexpression. After 16 months, histological abnormalities were exclusively observed in the retina of E50K mutant mice with loss of RGCs and connecting synapses in the peripheral retina leading to a thinning of the nerve fiber layer at the optic nerve head at normal IOP. E50K mice also showed massive apoptosis and degeneration of entire retina, leading to approximately a 28% reduction of the retina thickness. At the molecular level, introduction of the E50K mutation disrupts the interaction between Optn and Rab8 GTPase, a protein involved in the regulation of vesicle transport from Golgi to plasma membrane. Wt Optn and an active GTP-bound form of Rab8 complex were localized at the Golgi complex. These data suggest that alternation of the Optn sequence can initiate significant retinal degeneration in mice. PMID:20388642

  2. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS

    PubMed Central

    Koch, J C; Tönges, L; Barski, E; Michel, U; Bähr, M; Lingor, P

    2014-01-01

    The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy. PMID:24832597

  3. Compound 49b Restores Retinal Thickness and Reduces Degenerate Capillaries in the Rat Retina following Ischemia/Reperfusion

    PubMed Central

    Liu, Li; Jiang, Youde

    2016-01-01

    We have recently reported that Compound 49b, a novel β-adrenergic receptor agonist, can significantly reduce VEGF levels in retinal endothelial cells (REC) grown in diabetic-like conditions. In this study, we investigated whether Compound 49b could protect the retina under hypoxic conditions using the ischemia-reperfusion (I/R)-induced model in rats, as well REC cultured in hypoxic conditions. Some rats received 1mM topical Compound 49b for the 2 (5 rats each group) or 10 (4 rats in each group) days post-I/R. Analyses for retinal thickness and cell loss in the ganglion cell layer was done at 2 days post-I/R, while numbers of degenerate capillaries and pericyte ghosts were measured at 10 days post-I/R. Additionally, REC were cultured in normal oxygen or hypoxia (5% O2) only or treated with 50 nM Compound 49b for 12 hours. Twelve hours after Compound 49b exposure, cells were collected and analyzed for protein levels of insulin-like growth factor binding protein 3 (IGFBP-3), vascular endothelial cell growth factor (VEGF) and its receptor (KDR), angiopoietin 1 and its receptor Tie2 for Western blotting. Data indicate that exposure to I/R significantly decreased retinal thickness, with increasing numbers of degenerate capillaries and pericyte ghosts. Compound 49b treatment inhibited these retinal changes. In REC cultured in hypoxia, levels of IGFBP-3 were reduced, which were significantly increased by Compound 49b. Hypoxia significantly increased protein levels of VEGF, KDR, Angiopoiein 1, and Tie2, which were reduced following Compound 49b treatment. These data strongly suggested that Compound 49b protected the retina against I/R-induced injury. This provides additional support for a role of β-adrenergic receptor actions in the retina. PMID:27439004

  4. Rotatory subluxation of the scaphoid after excision of dorsal carpal ganglion and wrist manipulation--a case report.

    PubMed

    Crawford, G P; Taleisnik, J

    1983-11-01

    Surgical excision of a ganglion on the dorsum of the wrist is usually a benign procedure. The most frequent complications are transient postoperative stiffness and recurrence of the ganglion. This paper reports the development of a rotatory subluxation of the scaphoid after the manipulation of the wrist of a patient who had developed postoperative stiffness after the surgical excision of a dorsal wrist ganglion. This unusual complication was successfully treated by closed pinning under radiographic control followed by immobilization in palmar flexion. Manipulation of the wrist for the management of postoperative stiffness is rarely, if ever, indicated. Limitation of motion of a wrist without underlying structural changes is best managed by gentle, gradual splinting, both static and dynamic. It is suggested that preoperative x-rays should be obtained as part of the routine workup for a dorsal wrist ganglion.

  5. Percutaneous ultrasound-guided aspiration of an anterior cruciate ligament ganglion cyst: description of technique and case presentation.

    PubMed

    Krill, Michael; Peck, Evan

    2014-12-01

    An anterior cruciate ligament ganglion cyst is an infrequent but potentially clinically significant cause of knee pain. Although the cyst may be removed surgically, percutaneous ultrasound-guided anterior cruciate ligament ganglion cyst aspiration and injection is feasible. To our knowledge, we present the first reported case description of the utilization of ultrasound guidance to perform this procedure with a successful clinical outcome. PMID:25088315

  6. Transplantation of human adipose tissue-derived stem cells for repair of injured spiral ganglion neurons in deaf guinea pigs.

    PubMed

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Cho, Yong-Bum; Park, Jong-Seong; Jeong, Han-Seong

    2016-06-01

    Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells (ADSCs) for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs (NI-hADSCs) can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-hADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks' balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-hADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-hADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 dB of clicks or pure tone burst. These findings suggest that a large amount of NI-hADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs. PMID:27482231

  7. Transplantation of human adipose tissue-derived stem cells for repair of injured spiral ganglion neurons in deaf guinea pigs

    PubMed Central

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Cho, Yong-Bum; Park, Jong-Seong; Jeong, Han-Seong

    2016-01-01

    Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells (ADSCs) for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs (NI-hADSCs) can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-hADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks’ balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-hADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-hADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 dB of clicks or pure tone burst. These findings suggest that a large amount of NI-hADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs. PMID:27482231

  8. Site of origin and mechanism of action of adenosine in the frog sympathetic ganglion

    SciTech Connect

    Bencherif, M.

    1987-01-01

    The contribution of pre and postsynaptic activation on the release of {sup 3}H-purines was studied in the isolated sympathetic paravertebral ganglion of the frog. Preganglionic stimulation induced an overall release of {sup 3}H-purines. This release is blocked by atropine and curare and can be induced by carbachol and antidromic stimulation. Analyses of the effluent by anion exchange chromatography and by HPLC showed that the non-nucleotide fractions constituted most of the counts released. Hence, nucleosides are the main products released by the ganglion and did not arise from hydrolysis of extracellular ATP. We studied the effect of synaptic activity on tritiated inositol release (IR). This release did not change during orthodromic stimulation. However, upon cessation of the stimulation, release increased rapidly and remained elevated for at least 45 minutes. This increase in IR was reduced by suffusion of the ganglia with either acetylcholine or adenosine.

  9. Lethal effect of the serotonin-xylocaineR association in ganglion-blocked rats.

    PubMed

    Valle, L B; Oliveira-Filho, R M; Armonia, P L; Saraceni, G; Nassif, M; De Lucia, R

    1976-12-01

    In rats anestetized with urethane and under ganglionic blockade by hexamethonium (20 mg/kg, i.v.), the i.v. injection of serotonin (60 mug/kg) determined apnea, ECG alterations and a brief hypotensive response which is similar to that as elicited when 5-HT is given to intact rats. During the hypertension which follows that initial response, apnea is still present along with more severe ECG changes. After that, blood pressure falls into a prolonged hypotension, which is invariably accompanied by death. Neither norepinephrine, nor respiratory analeptics (CoramineR, RemeflinF) were able to prevent the fatal outcome. Only artificial respiration was found to be useful in some instances. It was concluded that the association serotonin plus lidocaine becomes lethal when given to ganglion-blocked rate, and this toxic effect can be ascribed mainly to the respiratory depressor activity of the drugs.

  10. Unilateral reduction of head pain and facial vasodilatation after gasserian ganglion lesion.

    PubMed

    De Marinis, M; Fraioli, B; Esposito, V; Gagliardi, F M; Agnoli, A

    1993-02-01

    The features of histamine-induced headache and its associated vascular responses were studied in 52 patients with different surgical lesions of the gasserian ganglion and in 12 control subjects. Certain features of headache (eg, intensity, type, and duration) were similar in patients and control subjects. However, the pain was absent on the side of the trigeminal lesion in 26 (50%) of the patients. This unilateral absence of pain was not related to the hypoesthesia that was caused by the operation, and it was associated with a decrease in vascular responses (histamine-induced facial flushing and increase in temperature) on the side operated on. These abnormalities were more prevalent in patients who had undergone thermocoagulation and presented with more severe damage of the trigeminal ganglion than in those who were subjected to trigeminal compression or glycerolization. The trigemino-vascular system seems to control headache of a vascular type and associated craniofacial vasodilatation in human subjects.

  11. The pterygopalatine ganglion and its role in various pain syndromes: from anatomy to clinical practice.

    PubMed

    Piagkou, Maria; Demesticha, Theano; Troupis, Theodore; Vlasis, Konstantinos; Skandalakis, Panayiotis; Makri, Aggeliki; Mazarakis, Antonios; Lappas, Dimitrios; Piagkos, Giannoulis; Johnson, Elizabeth O

    2012-06-01

    The postsynaptic fibers of the pterygopalatine or sphenopalatine ganglion (PPG or SPG) supply the lacrimal and nasal glands. The PPG appears to play an important role in various pain syndromes including headaches, trigeminal and sphenopalatine neuralgia, atypical facial pain, muscle pain, vasomotor rhinitis, eye disorders, and herpes infection. Clinical trials have shown that these pain disorders can be managed effectively with sphenopalatine ganglion blockade (SPGB). In addition, regional anesthesia of the distribution area of the SPG sensory fibers for nasal and dental surgery can be provided by SPGB via a transnasal, transoral, or lateral infratemporal approach. To arouse the interest of the modern-day clinicians in the use of the SPGB, the advantages, disadvantages, and modifications of the available methods for blockade are discussed.▪

  12. Fireworks in the primate retina: in vitro photodynamics reveals diverse LGN-projecting ganglion cell types.

    PubMed

    Dacey, Dennis M; Peterson, Beth B; Robinson, Farrel R; Gamlin, Paul D

    2003-01-01

    Diverse cell types and parallel pathways are characteristic of the vertebrate nervous system, yet it remains a challenge to define the basic components of most neural structures. We describe a process termed retrograde photodynamics that allowed us to rapidly make the link between morphology, physiology, and connectivity for ganglion cells in the macaque retina that project to the lateral geniculate nucleus (LGN). Rhodamine dextran injected into the LGN was transported retrogradely and sequestered within the cytoplasm of ganglion cell bodies. Exposure of the retina to light in vitro liberated the tracer and allowed it to diffuse throughout the dendrites, revealing the cell's complete morphology. Eight previously unknown LGN-projecting cell types were identified. Cells could also be targeted in vitro for intracellular recording and physiological analysis. The photodynamic process was also observed in pyramidal cells in a rat neocortical slice.

  13. A ganglion cyst causing lumbar radiculopathy in a baseball pitcher: a case report.

    PubMed

    Lee, J; Wisneski, R J; Lutz, G E

    2000-06-01

    This report describes a case of a professional baseball pitcher who developed acute left lumbar radicular symptoms after a baseball game and was subsequently sidelined for the rest of the season. Physical examination revealed depressed reflexes in the left posterior tibialis and left medial hamstring muscles, mild weakness in the left extensor hallucis longus, and positive dural tension signs. Magnetic resonance imaging demonstrated an ovoid mass at the L4-L5 level, causing compression of the dura. Surgical resection of the mass resulted in resolution of his symptoms. Pathology revealed that the mass was a ganglion cyst. A ganglion cyst is a rare cause of lumbar radiculopathy and should be considered in the differential diagnosis if a patient with lumbar radiculopathy fails to respond to conservative treatment.

  14. Clinical functional anatomy of the pterygopalatine ganglion, cephalgia and related dysautonomias: A review

    PubMed Central

    Khonsary, Seyed Ali; Ma, Quanfeng; Villablanca, Pablo; Emerson, Josh; Malkasian, Dennis

    2013-01-01

    The purpose of this article is to explain the anatomy of the pterygopalatine ganglion (PPG), its location in the pterygopalatine fossa (PPF) in the skull, and the relationship it has to the Vidian nerve terminal branches and the fifth cranial nerve. An overview of the neuro-anatomical/clinical correlations, a spectrum of pathologies affecting the seventh cranial nerve and some therapies both medical and surgical are noted. The focus is the pterygopalatine region with discussion of the proximal courses of the seventh and fifth cranial nerves and their pathological processes. The ganglion is used as an example of neuro-anatomical model for explaining cluster headaches (CH). Radiological correlation is included to clarify the location of the PPF and its clinical importance. PMID:24349865

  15. Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier.

    PubMed

    Froud, Kristina E; Wong, Ann Chi Yan; Cederholm, Jennie M E; Klugmann, Matthias; Sandow, Shaun L; Julien, Jean-Pierre; Ryan, Allen F; Housley, Gary D

    2015-01-01

    The dynamic adjustment of hearing sensitivity and frequency selectivity is mediated by the medial olivocochlear efferent reflex, which suppresses the gain of the 'cochlear amplifier' in each ear. Such efferent feedback is important for promoting discrimination of sounds in background noise, sound localization and protecting the cochleae from acoustic overstimulation. However, the sensory driver for the olivocochlear reflex is unknown. Here, we resolve this longstanding question using a mouse model null for the gene encoding the type III intermediate filament peripherin (Prph). Prph((-/-)) mice lacked type II spiral ganglion neuron innervation of the outer hair cells, whereas innervation of the inner hair cells by type I spiral ganglion neurons was normal. Compared with Prph((+/+)) controls, both contralateral and ipsilateral olivocochlear efferent-mediated suppression of the cochlear amplifier were absent in Prph((-/-)) mice, demonstrating that outer hair cells and their type II afferents constitute the sensory drive for the olivocochlear efferent reflex.

  16. Idiopathic myenteric ganglionitis underlying acute 'dramatic' intestinal pseudoobstruction: report of an exceptional case.

    PubMed

    Racalbuto, A; Magro, G; Lanteri, R; Aliotta, I; Santangelo, M; Di Cataldo, A

    2008-09-01

    Inflammation of the myenteric plexus of the gastrointestinal tract is a very rare pathological condition, with few reports in the medical literature. This pathological condition causes atonic gut motor dysfunction and is principally secondary to other diseases, being reported nearly solely as a paraneoplastic phenomenon in neuroendocrine lung tumors, including small cell carcinomas or neuroblastomas. In addition it can also be associated with disorders of the central nervous system, although it has rarely been described in Chagas disease. It has been named 'idiopathic myenteric ganglionitis' because no apparent causes can be demonstrated. We report the clinicopathologic findings of an exceptional case of a young woman affected by severe chronic constipation suddenly changing into acute intestinal pseudoobstruction with dramatic evolution. Relationships between ganglionitis, idiopathic constipation and acute intestinal pseudoobstruction as well as therapeutic implications are discussed.

  17. [The concept of "ganglionitis" in the modern science of the autonomic nervous system].

    PubMed

    Veĭn, A M; Golubev, V L; Alimova, E Ia; Danilov, A B

    1990-01-01

    The authors review the concept of vegetative "ganglionitis" formed in the Soviet literature in the 40-60s. Consider the etiological, clinical and diagnostic aspects thereof. Provide the modern concepts of the clinical manifestations related to the lesions of the paravertebral sympathetic ganglia. Relate some hypotheses concerning the origin of painful phenomena within the framework of the syndrome of reflex sympathetic dystrophy. Indicate that verified lesions of the sympathetic ganglia are associated with well-defined clinical symptoms which absolutely differ in their appearance from the reported descriptions of "ganglionitis", which are unjustifiedly widely used in the Soviet literature over the recent decades. The conclusion is made about the necessity of reviewing the outdated concepts of the pathology of the vegetative sympathetic ganglia from the standpoint of the modern concept of peripheral vegetative insufficiency.

  18. Drosophila Lin-7 is a component of the Crumbs complex in epithelia and photoreceptor cells and prevents light-induced retinal degeneration.

    PubMed

    Bachmann, André; Grawe, Ferdi; Johnson, Kevin; Knust, Elisabeth

    2008-03-01

    The Drosophila Crumbs protein complex is required to maintain epithelial cell polarity in the embryo, to ensure proper morphogenesis of photoreceptor cells and to prevent light-dependent retinal degeneration. In Drosophila, the core components of the complex are the transmembrane protein Crumbs, the membrane-associated guanylate kinase (MAGUK) Stardust and the scaffolding protein DPATJ. The composition of the complex and some of its functions are conserved in mammalian epithelial and photoreceptor cells. Here, we report that Drosophila Lin-7, a scaffolding protein with one Lin-2/Lin-7 (L27) domain and one PSD-95/Dlg/ZO-1 (PDZ) domain, is associated with the Crumbs complex in the subapical region of embryonic and follicle epithelia and at the stalk membrane of adult photoreceptor cells. DLin-7 loss-of-function mutants are viable and fertile. While DLin-7 localization depends on Crumbs, neither Crumbs, Stardust nor DPATJ require DLin-7 for proper accumulation in the subapical region. Unlike other components of the Crumbs complex, DLin-7 is also enriched in the first optic ganglion, the lamina, where it co-localizes with Discs large, another member of the MAGUK family. In contrast to crumbs mutant photoreceptor cells, those mutant for DLin-7 do not display any morphogenetic abnormalities. Similar to crumbs mutant eyes, however, DLin-7 mutant photoreceptors undergo progressive, light-dependent degeneration. These results support the previous conclusions that the function of the Crumbs complex in cell survival is independent from its function in photoreceptor morphogenesis.

  19. An Unusual Case of Extensive Lattice Degeneration and Retinal Detachment

    PubMed Central

    Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V.

    2016-01-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were also areas of white without pressure, chorioretinal scarring and retinal breaks. All the changes were limited to beyond the equator but were found to span 360 degrees. She was treated with barrage laser all around to prevent extension of the retinal detachment posteriorly. She remained stable till her latest follow-up two years after the barrage laser. This case is reported for its rarity with a discussion of the probable differential diagnoses. To the best of our knowledge, this is the first report of such findings in lattice degeneration.

  20. Hypertrophic olivary degeneration and cerebrovascular disease: movement in a triangle.

    PubMed

    Santos, Ana Filipa; Rocha, Sofia; Varanda, Sara; Pinho, João; Rodrigues, Margarida; Ramalho Fontes, João; Soares-Fernandes, João; Ferreira, Carla

    2015-02-01

    Hypertrophic olivary degeneration is a rare kind of trans-synaptic degeneration that occurs after lesions of the dentatorubro-olivary pathway. The lesions, commonly unilateral, may result from hemorrhage due to vascular malformation, trauma, surgical intervention or hypertension, tumor, or ischemia. Bilateral cases are extremely rare. This condition is classically associated with development of palatal tremor, but clinical manifestations can include other involuntary movements. We describe 2 cases: unilateral hypertrophic olivary degeneration in a 60-year-old man with contralateral athetosis and neurologic worsening developing several years after a pontine hemorrhage and bilateral hypertrophic olivary degeneration in a 77-year-old woman with development of palatal tremor, probably secondary to pontine ischemic lesions (small vessel disease).

  1. [Progress on the degeneration mechanism of cave fishes' eyes].

    PubMed

    Gu, Xian; Ning, Tiao; Xiao, Heng

    2012-08-01

    Attempts to understand the degeneration of the eyes in cave fish has largely been explained by either various extents of gradual degeneration, ranging from partial to total loss, observed in various species or by acceleration of loss caused by dark environments. However, neither the theory of biological evolution developed by Charles Darwin nor the neutral theory of molecular evolution formulated by Kimura Motoo adequately explains these phenomena. Recent trends in utilizing multidisciplinary research, however, have yielded better results, helping reveal a more complex picture of the mechanisms of degeneration. Here, we summarize the current progress of the research via morphology and anatomy, development biology, animal behavior science and molecular genetics, and offer some perspectives on the ongoing research into the development and degeneration of eyes in cave fish.

  2. Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration.

    PubMed

    Zhao, Lian; Zabel, Matthew K; Wang, Xu; Ma, Wenxin; Shah, Parth; Fariss, Robert N; Qian, Haohua; Parkhurst, Christopher N; Gan, Wen-Biao; Wong, Wai T

    2015-07-02

    Retinitis pigmentosa, caused predominantly by mutations in photoreceptor genes, currently lacks comprehensive treatment. We discover that retinal microglia contribute non-cell autonomously to rod photoreceptor degeneration by primary phagocytosis of living rods. Using rd10 mice, we found that the initiation of rod degeneration is accompanied by early infiltration of microglia, upregulation of phagocytic molecules in microglia, and presentation of "eat-me" signals on mutated rods. On live-cell imaging, infiltrating microglia interact dynamically with photoreceptors via motile processes and engage in rapid phagocytic engulfment of non-apoptotic rods. Microglial contribution to rod demise is evidenced by morphological and functional amelioration of photoreceptor degeneration following genetic ablation of retinal microglia. Molecular inhibition of microglial phagocytosis using the vitronectin receptor antagonist cRGD also improved morphological and functional parameters of degeneration. Our findings highlight primary microglial phagocytosis as a contributing mechanism underlying cell death in retinitis pigmentosa and implicate microglia as a potential cellular target for therapy.

  3. Three forms of spatial temporal feedforward inhibition are common to different ganglion cell types in rabbit retina.

    PubMed

    Chen, Xin; Hsueh, Hain-Ann; Greenberg, Kenneth; Werblin, Frank S

    2010-05-01

    There exist more than 30 different morphological amacrine cell types, but there may be fewer physiological types. Here we studied the amacrine cell outputs by measuring the temporal and spatial properties of feedforward inhibition to four different types of ganglion cells. These ganglion cells, each with concentric receptive field organization, appear to receive a different relative contribution of the same three forms of feed-forward inhibition, namely: local glycinergic, local sustained GABAergic, and broad transient GABAergic inhibition. Two of these inhibitory components, local glycinergic inhibition and local sustained GABAergic inhibition were localized to narrow regions confined to the dendritic fields of the ganglion cells. The third, a broad transient GABAergic inhibition, was driven from regions peripheral to the dendritic area. Each inhibitory component is also correlated with characteristic kinetics expressed in all ganglion cells: broad transient GABAergic inhibition had the shortest latency, local glycinergic inhibition had an intermediate latency, and local sustained GABAergic inhibition had the longest latency. We suggest each of these three inhibitory components represents the output from a distinct class of amacrine cell, mediates a specific visual function, and each forms a basic functional component for the four ganglion cell types. Similar subunits likely exist in the circuits of other ganglion cell types as well.

  4. A phospholipase A₂ isolated from Lachesis muta snake venom increases the survival of retinal ganglion cells in vitro.

    PubMed

    da Silva Cunha, Karinne Cristinne; Fuly, André Lopes; de Araujo, Elizabeth Giestal

    2011-03-15

    We have previously showed that a phospholipase A₂ isolated from Lachesis muta snake venom and named LM-PLA₂-I displayed particular biological activities, as hemolysis, inhibition on platelet aggregation, edema induction and myotoxicity. In the present work, we evaluated the effect of LM-PLA₂-I on the survival of axotomized rat retinal ganglion cells kept in vitro, as well as its mechanism of action. Our results clearly showed that treatment with LM-PLA₂-I increased the survival of ganglion cells (100% when compared to control cultures) and the treatment of LM-PLA₂-I with p-bromophenacyl bromide abolished this effect. This result indicates that the effect of LM-PLA₂-I on ganglion cell survival is entirely dependent on its enzymatic activity and the generation of lysophosphatidylcholine (LPC) may be a prerequisite to the observed survival. In fact, commercial LPC mimicked the effect of LM-PLA₂-I upon ganglion cell survival. To investigate the mechanism of action of LM-PLA₂-I, cultures were treated with chelerythrine chloride, BAPTA-AM, rottlerin and also with an inhibitor of c-junc kinase (JNKi). Our results showed that rottlerin and JNK inhibitor abolished the LM-PLA₂-I on ganglion cell survival. Taken together, our results showed that LM-PLA₂-I and its enzymatic product, LPC promoted survival of retinal ganglion cells through the protein kinase C pathway and strongly suggest a possible role of the PLA₂ enzyme and LPC in controlling the survival of axotomized neuronal cells. PMID:21223976

  5. Specific projection of displaced retinal ganglion cells upon the accessory optic system in the pigeon (Columbia livia).

    PubMed

    Karten, J H; Fite, K V; Brecha, N

    1977-04-01

    In the pigeon, the nucleus of the basal optic root, a component of the accessory optic system, projects directly upon the vestibulo-cerebellum. This nucleus receives a prominent projection composed of large-diameter retinal axons, known as the basal optic root. The cells of origin of this tract were identified using horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) as a retrograde marker. Injections of horseradish peroxidase confined primarily to the basal optic root nucleus labeled displaced ganglion cells of the contralateral retina. Cell sizes were 18-30 micronm and the dendrites of these cells were confined to the first stratum of the inner plexiform layer. Approximately 3700 displaced ganglion cells were labeled after injections of horseradish peroxidase into basal optic root. In contrast, no displaced ganglion cells were labeled after injections of horseradish peroxidase into the optic tectum, which labeled only cells in the ganglion cell layer proper. These findings indicate that displaced ganglion cells constitute a unique population of retinal neurons that give rise to a bisynaptic pathway directed to the cerebellum via the nucleus of the basal optic root. These displaced ganglion cells may play a major role inoculomotor reflexes.

  6. Frontotemporal Lobar Degeneration and MicroRNAs

    PubMed Central

    Piscopo, Paola; Albani, Diego; Castellano, Anna E.; Forloni, Gianluigi; Confaloni, Annamaria

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) includes a spectrum of disorders characterized by changes of personality and social behavior and, often, a gradual and progressive language dysfunction. In the last years, several efforts have been fulfilled in identifying both genetic mutations and pathological proteins associated with FTLD. The molecular bases undergoing the onset and progression of the disease remain still unknown. Recent literature prompts an involvement of RNA metabolism in FTLD, particularly microRNAs (miRNAs). Dysregulation of miRNAs in several disorders, including neurodegenerative diseases, and increasing importance of circulating miRNAs in different pathologies has suggested to implement the study of their possible application as biological markers and new therapeutic targets; moreover, miRNA-based therapy is becoming a powerful tool to deepen the function of a gene, the mechanism of a disease, and validate therapeutic targets. Regarding FTLD, different studies showed that miRNAs are playing an important role. For example, several reports have evaluated miRNA regulation of the progranulin gene suggesting that it is under their control, as described for miR-29b, miR-107, and miR-659. More recently, it has been demonstrated that TMEM106B gene, which protein is elevated in FTLD-TDP brains, is repressed by miR-132/212 cluster; this post-transcriptional mechanism increases intracellular levels of progranulin, affecting its pathways. These findings if confirmed could suggest that these microRNAs have a role as potential targets for some related-FTLD genes. In this review, we focus on the emerging roles of the miRNAs in the pathogenesis of FTLD. PMID:26903860

  7. Distinct optical properties of relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2014-06-15

    In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.

  8. The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

    PubMed

    Kamo, Atsuko; Tominaga, Mitsutoshi; Kamata, Yayoi; Kaneda, Kazuyuki; Ko, Kyi C; Matsuda, Hironori; Kimura, Utako; Ogawa, Hideoki; Takamori, Kenji

    2014-12-01

    Epidermal hyperinnervation, which is thought to underlie intractable pruritus, has been observed in patients with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. Previously, we showed that the excimer lamp has antihyperinnervative effects in nonpruritic dry-skin model mice, although epidermal expression of axonal guidance molecules was unchanged. Therefore, we investigated the antipruritic effects of excimer lamp irradiation and its mechanism of action. A single irradiation of AD model mice significantly inhibited itch-related behavior 1 day later, following improvement in the dermatitis score. In addition, irradiation of nerve fibers formed by cultured dorsal root ganglion neurons increased bleb formation and decreased nerve fiber expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting degenerative changes in these fibers. We also analyzed whether attaching a cutoff excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA damage marker, in dry-skin model mice. Irradiation with COF decreased CPD production in keratinocytes, as well as having an antihyperinnervative effect, indicating that the antipruritic effects of excimer lamp irradiation with COF are due to induction of epidermal nerve degeneration and reduced DNA damage. PMID:24940652

  9. The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

    PubMed

    Kamo, Atsuko; Tominaga, Mitsutoshi; Kamata, Yayoi; Kaneda, Kazuyuki; Ko, Kyi C; Matsuda, Hironori; Kimura, Utako; Ogawa, Hideoki; Takamori, Kenji

    2014-12-01

    Epidermal hyperinnervation, which is thought to underlie intractable pruritus, has been observed in patients with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. Previously, we showed that the excimer lamp has antihyperinnervative effects in nonpruritic dry-skin model mice, although epidermal expression of axonal guidance molecules was unchanged. Therefore, we investigated the antipruritic effects of excimer lamp irradiation and its mechanism of action. A single irradiation of AD model mice significantly inhibited itch-related behavior 1 day later, following improvement in the dermatitis score. In addition, irradiation of nerve fibers formed by cultured dorsal root ganglion neurons increased bleb formation and decreased nerve fiber expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting degenerative changes in these fibers. We also analyzed whether attaching a cutoff excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA damage marker, in dry-skin model mice. Irradiation with COF decreased CPD production in keratinocytes, as well as having an antihyperinnervative effect, indicating that the antipruritic effects of excimer lamp irradiation with COF are due to induction of epidermal nerve degeneration and reduced DNA damage.

  10. Seasonally Changing Cryptochrome 1b Expression in the Retinal Ganglion Cells of a Migrating Passerine Bird.

    PubMed

    Nießner, Christine; Gross, Julia Christina; Denzau, Susanne; Peichl, Leo; Fleissner, Gerta; Wiltschko, Wolfgang; Wiltschko, Roswitha

    2016-01-01

    Cryptochromes, blue-light absorbing proteins involved in the circadian clock, have been proposed to be the receptor molecules of the avian magnetic compass. In birds, several cryptochromes occur: Cryptochrome 2, Cryptochrome 4 and two splice products of Cryptochrome 1, Cry1a and Cry1b. With an antibody not distinguishing between the two splice products, Cryptochrome 1 had been detected in the retinal ganglion cells of garden warblers during migration. A recent study located Cry1a in the outer segments of UV/V-cones in the retina of domestic chickens and European robins, another migratory species. Here we report the presence of cryptochrome 1b (eCry1b) in retinal ganglion cells and displaced ganglion cells of European Robins, Erithacus rubecula. Immuno-histochemistry at the light microscopic and electron microscopic level showed eCry1b in the cell plasma, free in the cytosol as well as bound to membranes. This is supported by immuno-blotting. However, this applies only to robins in the migratory state. After the end of the migratory phase, the amount of eCry1b was markedly reduced and hardly detectable. In robins, the amount of eCry1b in the retinal ganglion cells varies with season: it appears to be strongly expressed only during the migratory period when the birds show nocturnal migratory restlessness. Since the avian magnetic compass does not seem to be restricted to the migratory phase, this seasonal variation makes a role of eCry1b in magnetoreception rather unlikely. Rather, it could be involved in physiological processes controlling migratory restlessness and thus enabling birds to perform their nocturnal flights. PMID:26953690

  11. Chemically defined medium enhances bioelectric activity in mouse spinal cord-dorsal root ganglion cultures.

    PubMed

    Habets, A M; Baker, R E; Brenner, E; Romijn, H J

    1981-02-23

    Co-cultures of mouse spinal cord with dorsal root ganglion (DRG) cultures were grown either in horse serum (HS)-supplemented medium or in a serum-free, chemically defined medium (CDM). The cytoarchitecture of cord--DRG explants was fully retained in CDM, with little or no distortion due to flattening of the explant, as is invariably observed in HS-supplemented cultures. Functional properties such as bioelectric activity and DRG--spinal cord interconnectivity were well sustained in CDM.

  12. Characterization and localization of nerve growth factor receptors in the embryonic otic vesicle and cochleovestibular ganglion

    SciTech Connect

    Bernd, P.; Represa, J. )

    1989-07-01

    We have investigated the possibility that nerve growth factor (NGF) may play a role in the development of the inner ear. Primordia of the inner ear, the otic vesicle (OV) and cochleovestibular ganglion (CVG), were isolated from 72-hr (stage 19-20) quail embryos and examined for the presence of NGF receptors. Quantitative binding studies revealed that both OV and CVG exhibited specific 125I-NGF binding; levels of nonspecific binding were 6 to 26% of total binding. Scatchard analysis yielded a linear plot, indicating the presence of a single class of NGF receptor. The average binding constant (Kd) was 8.0 nM for OV and 8.6 nM for CVG, corresponding to the low affinity (site II) NGF receptor. Examination of light microscopic radioautographs indicated that most of the specific 125I-NGF binding was located in the ventromedial wall of the OV, with little or no binding in the lateral wall and endolymphatic primordia. These studies were corroborated by microdissection of OV, in which 70% of the radioactivity was found to be localized in the medial half of the OV. In CVG, specific 125I-NGF binding was more concentrated in the cochlear portion of the ganglion, with silver grains primarily over areas containing support cells and immature neurons. Quantitative binding studies with isolated cochlear and vestibular ganglia obtained from 144-hr (stage 29-30) quail embryos revealed that the cochlear ganglion exhibited three times more specific 125I-NGF binding than the vestibular ganglion. The presence of NGF receptors on OV and CVG suggests that these structures are responsive to and/or dependent upon NGF. The following paper examines the question of whether NGF serves either as a mitogen, a survival factor, or a differentiation factor in this system.

  13. Retinal ganglion cell density of the black rhinoceros (Diceros bicornis): calculating visual resolution.

    PubMed

    Pettigrew, John D; Manger, Paul R

    2008-01-01

    A single right retina from a black rhinoceros was whole mounted, stained and analyzed to determine the visual resolution of the rhinoceros, an animal with reputedly poor eyesight. A range of small (15-microm diameter) to large (100-microm diameter) ganglion cell types was seen across the retina. We observed two regions of high density of retinal ganglion cells at either end of a long, but thin, horizontal streak. The temporal specialization, which receives light from the anterior visual field, exhibited a ganglion cell density of approximately 2000/mm2, while the nasal specialization exhibited a density of approximately 1500/mm2. The retina exhibited a ganglion cell density bias toward the upper half, especially so, the upper temporal quadrant, indicating that the rhinoceros would be processing visual information from the visual field below the anterior horizon for the most part. Our calculations indicate that the rhinoceros has a visual resolution of 6 cycles/degree. While this resolution is one-tenth that of humans (60 cycles/deg) and less than that of the domestic cat (9 cycles/deg), it is comparable to that of the rabbit (6 cycles/deg), and exceeds that seen in a variety of other mammals including seals, dolphins, microbats, and rats. Thus, the reputation of the rhinoceros as a myopic, weakly visual animal is not supported by our observations of the retina. We calculate that the black rhinoceros could readily distinguish a 30 cm wide human at a distance of around 200 m given the appropriate visual background. PMID:18442443

  14. Autoradiographic measurement of relative changes in ornithine decarboxylase in axotomized superior cervical ganglion neurons

    SciTech Connect

    Wells, M.R.

    1986-05-01

    An autoradiographic method is described for detecting changes in ornithine decarboxylase in axotomized superior cervical ganglion neurons of rats using (3H)difluoromethylornithine. An increase in binding to neurons was seen at 12 h and 1 day after crushing the postganglionic nerves. Binding returned to control values between 3 and 5 days postoperation. The patterns found using this method were in general agreement with prior reports of enzymatic changes in whole ganglia.

  15. Growth interaction between locus coeruleus and trigeminal ganglion after intraocular double grafting.

    PubMed

    Seiger, A

    1980-06-01

    Fetal trigeminal ganglia were combined in the anterior chamber of eyes of rat recipients with sequentially grafted fetal locus coeruleus transplants. After maturation of both grafts in oculo the growth pattern of locus coeruleus derived noradrenaline fibres in the iris was examined with Falck-Hillarp fluorescence histochemistry. Contrary to what was expected from earlier studies, which revealed a radiating halo of fibres around the CNS tissue on the iris, the locus coeruleus-derived fibres radiated to a large extent from the adjacent trigeminal ganglion attachment. Thus, the presence of a grafted trigeminal ganglion changed the distribution of the central monoamine nerves growing out in the iris. The possible cause of this changed distribution is discussed. Maturated intraocular trigeminal ganglion transplants were retransplanted, together with the whole iris to which it was attached, into a new eye which already harboured a maturated locus coeruleus graft attached to its host iris. The expected reinitiated locus coeruleus fibre ingrowths into the iris transplants were then compared in those iris transplants that had trigeminal ganglia and controls that had not. The surface area of the iris grafts covered by newly formed locus coeruleus noradrenaline fibres was significantly smaller (27% reduction) if trigeminal ganglia were situated on them during the reinnervation process. This finding strongly supports our earlier studies, which suggested that the presence of sensory nerves in the iris inhibits growth of locus coeruleus in that receptor tissue, and furthermore, that the sensory nerves responsible for this inhibitory interaction have their origin within the trigeminal ganglion itself. PMID:7253725

  16. Scene from above: retinal ganglion cell topography and spatial resolving power in the giraffe (Giraffa camelopardalis).

    PubMed

    Coimbra, João Paulo; Hart, Nathan S; Collin, Shaun P; Manger, Paul R

    2013-06-15

    The giraffe (Giraffa camelopardalis) is a browser that uses its extensible tongue to selectively collect leaves during foraging. As the tallest extant terrestrial mammal, its elevated head height provides panoramic surveillance of the environment. These aspects of the giraffe's ecology and phenotype suggest that vision is of prime importance. Using Nissl-stained retinal wholemounts and stereological methods, we quantitatively assessed the retinal specializations in the ganglion cell layer of the giraffe. The mean total number of retinal ganglion cells was 1,393,779 and their topographic distribution revealed the presence of a horizontal visual streak and a temporal area. With a mean peak of 14,271 cells/mm(2), upper limits of spatial resolving power in the temporal area ranged from 25 to 27 cycles/degree. We also observed a dorsotemporal extension (anakatabatic area) that tapers toward the nasal retina giving rise to a complete dorsal arch. Using neurofilament-200 immunohistochemistry, we also detected a dorsal arch formed by alpha ganglion cells with density peaks in the temporal (14-15 cells/mm(2)) and dorsonasal (10 cells/mm(2)) regions. As with other artiodactyls, the giraffe shares the presence of a horizontal streak and a temporal area which, respectively, improve resolution along the horizon and in the frontal visual field. The dorsal arch is related to the giraffe's head height and affords enhanced resolution in the inferior visual field. The alpha ganglion cell distribution pattern is unique to the giraffe and enhances acquisition of motion information for the control of tongue movement during foraging and the detection of predators. PMID:23595815

  17. Connecting the eye to the brain: the molecular basis of ganglion cell axon guidance

    PubMed Central

    Oster, S F; Sretavan, D W

    2003-01-01

    In the past several years, a great deal has been learnt about the molecular basis through which specific neural pathways in the visual system are established during embryonic development. This review provides a framework for understanding the principles of retinal ganglion cell axon guidance, and introduces some of the families of axon guidance molecules involved. In addition, the potential relevance of retinal axon guidance to human visual developmental disorders, and to retinal axon regeneration, is discussed. PMID:12714414

  18. Seasonally Changing Cryptochrome 1b Expression in the Retinal Ganglion Cells of a Migrating Passerine Bird

    PubMed Central

    Nießner, Christine; Gross, Julia Christina; Denzau, Susanne; Peichl, Leo; Fleissner, Gerta; Wiltschko, Wolfgang; Wiltschko, Roswitha

    2016-01-01

    Cryptochromes, blue-light absorbing proteins involved in the circadian clock, have been proposed to be the receptor molecules of the avian magnetic compass. In birds, several cryptochromes occur: Cryptochrome 2, Cryptochrome 4 and two splice products of Cryptochrome 1, Cry1a and Cry1b. With an antibody not distinguishing between the two splice products, Cryptochrome 1 had been detected in the retinal ganglion cells of garden warblers during migration. A recent study located Cry1a in the outer segments of UV/V-cones in the retina of domestic chickens and European robins, another migratory species. Here we report the presence of cryptochrome 1b (eCry1b) in retinal ganglion cells and displaced ganglion cells of European Robins, Erithacus rubecula. Immuno-histochemistry at the light microscopic and electron microscopic level showed eCry1b in the cell plasma, free in the cytosol as well as bound to membranes. This is supported by immuno-blotting. However, this applies only to robins in the migratory state. After the end of the migratory phase, the amount of eCry1b was markedly reduced and hardly detectable. In robins, the amount of eCry1b in the retinal ganglion cells varies with season: it appears to be strongly expressed only during the migratory period when the birds show nocturnal migratory restlessness. Since the avian magnetic compass does not seem to be restricted to the migratory phase, this seasonal variation makes a role of eCry1b in magnetoreception rather unlikely. Rather, it could be involved in physiological processes controlling migratory restlessness and thus enabling birds to perform their nocturnal flights. PMID:26953690

  19. Single-degenerate Type Ia Supernovae Are Preferentially Overluminous

    NASA Astrophysics Data System (ADS)

    Fisher, Robert; Jumper, Kevin

    2015-06-01

    Recent observational and theoretical progress has favored merging and helium-accreting sub-Chandrasekhar mass white dwarfs (WDs) in the double-degenerate and the double-detonation channels, respectively, as the most promising progenitors of normal Type Ia supernovae (SNe Ia). Thus the fate of rapidly accreting Chandrasekhar mass WDs in the single-degenerate channel remains more mysterious then ever. In this paper, we clarify the nature of ignition in Chandrasekhar-mass single-degenerate SNe Ia by analytically deriving the existence of a characteristic length scale which establishes a transition from central ignitions to buoyancy-driven ignitions. Using this criterion, combined with data from three-dimensional simulations of convection and ignition, we demonstrate that the overwhelming majority of ignition events within Chandrasekhar-mass WDs in the single-degenerate channel are buoyancy-driven, and consequently lack a vigorous deflagration phase. We thus infer that single-degenerate SNe Ia are generally expected to lead to overluminous 1991T-like SNe Ia events. We establish that the rates predicted from both the population of supersoft X-ray sources (SSSs) and binary population synthesis models of the single-degenerate channel are broadly consistent with the observed rates of overluminous SNe Ia, and suggest that the population of SSSs are the dominant stellar progenitors of SNe 1991T-like events. We further demonstrate that the single-degenerate channel contribution to the normal and failed 2002cx-like rates is not likely to exceed 1% of the total SNe Ia rate. We conclude with a range of observational tests of overluminous SNe Ia which will either support or strongly constrain the single-degenerate scenario.

  20. SINGLE-DEGENERATE TYPE Ia SUPERNOVAE ARE PREFERENTIALLY OVERLUMINOUS

    SciTech Connect

    Fisher, Robert; Jumper, Kevin

    2015-06-01

    Recent observational and theoretical progress has favored merging and helium-accreting sub-Chandrasekhar mass white dwarfs (WDs) in the double-degenerate and the double-detonation channels, respectively, as the most promising progenitors of normal Type Ia supernovae (SNe Ia). Thus the fate of rapidly accreting Chandrasekhar mass WDs in the single-degenerate channel remains more mysterious then ever. In this paper, we clarify the nature of ignition in Chandrasekhar-mass single-degenerate SNe Ia by analytically deriving the existence of a characteristic length scale which establishes a transition from central ignitions to buoyancy-driven ignitions. Using this criterion, combined with data from three-dimensional simulations of convection and ignition, we demonstrate that the overwhelming majority of ignition events within Chandrasekhar-mass WDs in the single-degenerate channel are buoyancy-driven, and consequently lack a vigorous deflagration phase. We thus infer that single-degenerate SNe Ia are generally expected to lead to overluminous 1991T-like SNe Ia events. We establish that the rates predicted from both the population of supersoft X-ray sources (SSSs) and binary population synthesis models of the single-degenerate channel are broadly consistent with the observed rates of overluminous SNe Ia, and suggest that the population of SSSs are the dominant stellar progenitors of SNe 1991T-like events. We further demonstrate that the single-degenerate channel contribution to the normal and failed 2002cx-like rates is not likely to exceed 1% of the total SNe Ia rate. We conclude with a range of observational tests of overluminous SNe Ia which will either support or strongly constrain the single-degenerate scenario.

  1. Stochastic partial differential equations with unbounded and degenerate coefficients

    NASA Astrophysics Data System (ADS)

    Zhang, Xicheng

    In this article, using DiPerna-Lions theory (DiPerna and Lions, 1989) [1], we investigate linear second order stochastic partial differential equations with unbounded and degenerate non-smooth coefficients, and obtain several conditions for existence and uniqueness. Moreover, we also prove the L-integrability and a general maximal principle for generalized solutions of SPDEs. As applications, we study nonlinear filtering problem and also obtain the existence and uniqueness of generalized solutions for a degenerate nonlinear SPDE.

  2. Anterior cruciate ligament ganglion causing flexion restriction: a case report and review of literature

    PubMed Central

    Koh, Thean Howe Bryan; Lee, Keng Thiam

    2016-01-01

    Ganglion cysts originating from the anterior cruciate ligament (ACL) are uncommon. Often asymptomatic, they infrequently present with non-specific symptoms such as knee pain, stiffness, clicks, locking or restriction of knee extension. However, the patient we report presented with knee flexion restriction. A 37-year-old Chinese gentleman, with no history of knee trauma, presented with left knee pain. Left knee range of motion (ROM) was from 0 to 110 degrees. Magnetic resonance imaging (MRI) scan revealed a 1.5 cm × 3.3 cm × 1.7 cm cyst located in the intercondylar region arising from the ACL and extending predominantly posteriorly. Arthroscopy confirmed an intrasubstance ACL ganglion cyst, which was extending posteriorly. Complete excision of the cyst was performed. At 1-year follow-up, the patient regained knee flexion of 130 degrees. We describe one of the largest ACL ganglion cysts. Such cysts often extend anteriorly and impinge onto the roof of the intercondylar notch during knee extension, thus restricting extension. The restriction in knee motion in our patient was in flexion instead; this was because the cyst took an unusual course of extension predominantly in the posterior direction. Although rare, it must be included as a possible differential diagnosis when patients present with such knee symptoms. PMID:27386493

  3. Functional segregation of retinal ganglion cell projections to the optic tectum of rainbow trout.

    PubMed

    Novales Flamarique, Iñigo; Wachowiak, Matt

    2015-11-01

    The interpretation of visual information relies on precise maps of retinal representation in the brain coupled with local circuitry that encodes specific features of the visual scenery. In nonmammalian vertebrates, the main target of ganglion cell projections is the optic tectum. Although the topography of retinotectal projections has been documented for several species, the spatiotemporal patterns of activity and how these depend on background adaptation have not been explored. In this study, we used a combination of electrical and optical recordings to reveal a retinotectal map of ganglion cell projections to the optic tectum of rainbow trout and characterized the spatial and chromatic distribution of ganglion cell fibers coding for increments (ON) and decrements (OFF) of light. Recordings of optic nerve activity under various adapting light backgrounds, which isolated the input of different cone mechanisms, yielded dynamic patterns of ON and OFF input characterized by segregation of these two fiber types. Chromatic adaptation decreased the sensitivity and response latency of affected cone mechanisms, revealing their variable contributions to the ON and OFF responses. Our experiments further demonstrated restricted input from a UV cone mechanism to the anterolateral optic tectum, in accordance with the limited presence of UV cones in the dorsotemporal retina of juvenile rainbow trout. Together, our findings show that retinal inputs to the optic tectum of this species are not homogeneous, exhibit highly dynamic activity patterns, and are likely determined by a combination of biased projections and specific retinal cell distributions and their activity states. PMID:26334009

  4. Multiple Components of Ganglion Cell Desensitization in Response to Prosthetic Stimulation

    PubMed Central

    Freeman, Daniel K; Fried, Shelley I

    2011-01-01

    Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving neurons. Previous work indicates that repetitive stimulation with stimuli that activate the synaptic network reduces the sensitivity of retinal neurons to further stimulation. Such desensitization may contribute to the fading of visual percepts over time reported by human subjects. Here, we show that desensitization may be more complex than previously considered. We recorded spike trains from rabbit retinal ganglion cells and found that desensitization persists in the presence of inhibitory blockers (strychnine and picrotoxin), indicating amacrine cell inhibition is not solely responsible for reducing sensitivity in response to electric stimulation. The threshold for direct activation of the ganglion cell changes little during the simultaneous desensitization of the synaptically mediated response, indicating that desensitization likely occurs upstream of the spike generator. In addition to the rapid desensitization acting over hundreds of milliseconds (τ = 176.4 ± 8.8ms), we report the presence of a slow acting desensitization with a time course of seconds (τ = 14.0 ± 1.1sec). The time course of the two components of desensitization that we found are similar to the two phases of brightness fading seen in human subjects. This suggests that the reduction in ganglion cell firing due to desensitization may be responsible for the fading of visual percepts over time in response to prosthetic stimulation. PMID:21248379

  5. Moniliform deformation of retinal ganglion cells by formaldehyde-based fixatives.

    PubMed

    Stradleigh, Tyler W; Greenberg, Kenneth P; Partida, Gloria J; Pham, Aaron; Ishida, Andrew T

    2015-03-01

    Protocols for characterizing cellular phenotypes commonly use chemical fixatives to preserve anatomical features, mechanically stabilize tissue, and stop physiological responses. Formaldehyde, diluted in either phosphate-buffered saline or phosphate buffer, has been widely used in studies of neurons, especially in conjunction with dyes and antibodies. However, previous studies have found that these fixatives induce the formation of bead-like varicosities in the dendrites and axons of brain and spinal cord neurons. We report here that these formaldehyde formulations can induce bead formation in the dendrites and axons of adult rat and rabbit retinal ganglion cells, and that retinal ganglion cells differ from hippocampal, cortical, cerebellar, and spinal cord neurons in that bead formation is not blocked by glutamate receptor antagonists, a voltage-gated Na(+) channel toxin, extracellular Ca(2+) ion exclusion, or temperature shifts. Moreover, we describe a modification of formaldehyde-based fixatives that prevents bead formation in retinal ganglion cells visualized by green fluorescent protein expression and by immunohistochemistry.

  6. Inner retinal inhibition shapes the receptive field of retinal ganglion cells in primate

    PubMed Central

    Protti, D A; Di Marco, S; Huang, J Y; Vonhoff, C R; Nguyen, V; Solomon, S G

    2014-01-01

    Abstract The centre–surround organisation of receptive fields is a feature of most retinal ganglion cells (RGCs) and is critical for spatial discrimination and contrast detection. Although lateral inhibitory processes are known to be important in generating the receptive field surround, the contribution of each of the two synaptic layers in the primate retina remains unclear. Here we studied the spatial organisation of excitatory and inhibitory synaptic inputs onto ON and OFF ganglion cells in the primate retina. All RGCs showed an increase in excitation in response to stimulus of preferred polarity. Inhibition onto RGCs comprised two types of responses to preferred polarity: some RGCs showed an increase in inhibition whilst others showed removal of tonic inhibition. Excitatory inputs were strongly spatially tuned but inhibitory inputs showed more variable organisation: in some neurons they were as strongly tuned as excitation, and in others inhibitory inputs showed no spatial tuning. We targeted one source of inner retinal inhibition by functionally ablating spiking amacrine cells with bath application of tetrodotoxin (TTX). TTX significantly reduced the spatial tuning of excitatory inputs. In addition, TTX reduced inhibition onto those RGCs where a stimulus of preferred polarity increased inhibition. Reconstruction of the spatial tuning properties by somatic injection of excitatory and inhibitory synaptic conductances verified that TTX-mediated inhibition onto bipolar cells increases the strength of the surround in RGC spiking output. These results indicate that in the primate retina inhibitory mechanisms in the inner plexiform layer sharpen the spatial tuning of ganglion cells. PMID:24042496

  7. Response variability to high rates of electric stimulation in retinal ganglion cells.

    PubMed

    Cai, Changsi; Ren, Qiushi; Desai, Neal J; Rizzo, Joseph F; Fried, Shelley I

    2011-07-01

    To improve the quality of prosthetic vision, it is important to understand how retinal neurons respond to electric stimulation. Previous studies present conflicting reports as to the maximum rate at which retinal ganglion cells can "follow" pulse trains, i.e., generate one spike for each pulse of the train. In the present study, we measured the response of 5 different types of rabbit retinal ganglion cells to pulse trains of 100-700 Hz. Surprisingly, we found significant heterogeneity in the ability of different types to follow pulse trains. For example, brisk transient (BT) ganglion cells could reliably follow pulse rates up to 600 pulses per second (PPS). In contrast, other types could not even follow rates of 200 PPS. There was additional heterogeneity in the response patterns across those types that could not follow high-rate trains. For example, some types generated action potentials in response to approximately every other pulse, whereas other types generated one spike per pulse for a few consecutive pulses and then did not generate any spikes in response to the next few pulses. Interestingly, in the types that could not follow high-rate trains, we found a second type of response: many pulses of the train elicited a biphasic waveform with an amplitude much smaller than that of standard action potentials. This small waveform was often observed following every pulse for which a standard spike was not elicited. A possible origin of the small waveform and its implication for effective retinal stimulation are discussed.

  8. Multiple components of ganglion cell desensitization in response to prosthetic stimulation

    NASA Astrophysics Data System (ADS)

    Freeman, Daniel K.; Fried, Shelley I.

    2011-02-01

    Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving neurons. Previous work indicates that repetitive stimulation with stimuli that activate the synaptic network reduces the sensitivity of retinal neurons to further stimulation. Such desensitization may contribute to the fading of visual percepts over time reported by human subjects. Here, we show that desensitization may be more complex than previously considered. We recorded spike trains from rabbit retinal ganglion cells and found that desensitization persists in the presence of inhibitory blockers (strychnine and picrotoxin), indicating amacrine cell inhibition is not solely responsible for reducing sensitivity in response to electric stimulation. The threshold for direct activation of the ganglion cell changes little during the simultaneous desensitization of the synaptically mediated response, indicating that desensitization likely occurs upstream of the spike generator. In addition to rapid desensitization acting over hundreds of milliseconds (τ = 176.4 ± 8.8 ms), we report the presence of slow acting desensitization with a time course of seconds (τ = 14.0 ± 1.1 s). The time courses of the two components of desensitization that we found are similar to the two phases of brightness fading seen in human subjects. This suggests that the reduction in ganglion cell firing due to desensitization may be responsible for the fading of visual percepts over time in response to prosthetic stimulation.

  9. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

    Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

    2014-01-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  10. The Role of Cyclooxygenase in Multiplication and Reactivation of HSV-1 in Vestibular Ganglion Neurons

    PubMed Central

    Liu, Yuehong; Li, Shufeng; Wang, Zhengmin

    2014-01-01

    Reactivation of latent herpes simplex type 1 (HSV-1) and nerve inflammation have been shown to be involved in vertigo-related vestibular pathogenesis. Treatments of such diseases have been less than perfect. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to suppress reactivation of HSV-1 in trigeminal ganglions. However, whether this drug can affect reactivation of HSV-1 in vestibular ganglions is unclear. Due to the difficulties of constructing in vivo animal models, in this study, we developed a vestibular ganglion culture system, in which vestibular neurons were latently or lytically infected with HSV-1. Indomethacin and celecoxib were selected to measure their effects on HSV-1. Trichostatin A was used to reactivate HSV-1 in latently infected neurons. Cycloxygenase-2, which is the target of NSAIDs, was induced by HSV-1 in the lytically infected cultures, with an increase of 14-fold. Although it appeared that indomethacin and celecoxib showed limited but concentration-dependent inhibition effects on viral production under our condition, indomethacin decreased reactivation rate of HSV-1 by about 20%. Though more in vitro or in vivo studies are needed to confirm the effects of the drugs, our study may provide a potential way to investigate the mechanism of HSV-related vestibular pathogenesis as well as new treatments of vertigo-related diseases. PMID:24688447

  11. Organ of Corti explants direct tonotopically graded morphology of spiral ganglion neurons in vitro.

    PubMed

    Smith, Felicia L; Davis, Robin L

    2016-08-01

    The spiral ganglion is a compelling model system to examine how morphological form contributes to sensory function. While the ganglion is composed mainly of a single class of type I neurons that make simple one-to-one connections with inner hair cell sensory receptors, it has an elaborate overall morphological design. Specific features, such as soma size and axon outgrowth, are graded along the spiral contour of the cochlea. To begin to understand the interplay between different regulators of neuronal morphology, we cocultured neuron explants with peripheral target tissues removed from distinct cochlear locations. Interestingly, these "hair cell microisolates" were capable of both increasing and decreasing neuronal somata size, without adversely affecting survival. Moreover, axon characteristics elaborated de novo by the primary afferents in culture were systematically regulated by the sensory endorgan. Apparent peripheral nervous system (PNS)-like and central nervous system (CNS)-like axonal profiles were established in our cocultures allowing an analysis of putative PNS/CNS axon length ratios. As predicted from the in vivo organization, PNS-like axon bundles elaborated by apical cocultures were longer than their basal counterparts and this phenotype was methodically altered when neuron explants were cocultured with microisolates from disparate cochlear regions. Thus, location-dependent signals within the organ of Corti may set the "address" of neurons within the spiral ganglion, allowing them to elaborate the appropriate tonotopically associated morphological features in order to carry out their signaling function. J. Comp. Neurol. 524:2182-2207, 2016. © 2015 Wiley Periodicals, Inc.

  12. Moniliform Deformation of Retinal Ganglion Cells by Formaldehyde-Based Fixatives

    PubMed Central

    Stradleigh, Tyler W.; Greenberg, Kenneth P.; Partida, Gloria J.; Pham, Aaron; Ishida, Andrew T.

    2014-01-01

    Protocols for characterizing cellular phenotypes commonly use chemical fixatives to preserve anatomical features, mechanically stabilize tissue, and stop physiological responses. Formaldehyde, diluted in either phosphate-buffered saline or phosphate buffer, has been widely used in studies of neurons, especially in conjunction with dyes and antibodies. However, previous studies have reported that these fixatives induce the formation of bead-like varicosities in the dendrites and axons of brain and spinal cord neurons. We report here that these formaldehyde formulations can induce bead formation in the dendrites and axons of adult rat and rabbit retinal ganglion cells, and that retinal ganglion cells differ from hippocampal, cortical, cerebellar, and spinal cord neurons in that bead formation is not blocked by glutamate receptor antagonists, a voltage-gated Na+ channel toxin, extracellular Ca2+ ion exclusion, or temperature shifts. Moreover, we describe a modification of formaldehyde-based fixatives that prevents bead formation in retinal ganglion cells visualized by green fluorescent protein expression and by immunohistochemistry. PMID:25283775

  13. Prolonged Prevention of Retinal Degeneration with Retinylamine Loaded Nanoparticles

    PubMed Central

    Puntel, Anthony; Maeda, Akiko; Golczak, Marcin; Gao, Song-Qi; Yu, Guanping; Palczewski, Krzysztof; Lu, Zheng-Rong

    2015-01-01

    Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amines, including retinylamine, are effective in lowing the concentration of all-trans-retinal within the retina and thus prevent retina degeneration in mouse models of human retinopathies. Here we achieved prolonged prevention of retinal degeneration by controlled delivery of retinylamine to the eye from polylactic acid nanoparticles in Abca4−/−Rdh8−/− (DKO) mice, an animal model of Stargardt disease/age-related macular degeneration. Subcutaneous administration of the nanoparticles containing retinylamine provided a constant supply of the drug to the eye for about a week and resulted in effective prolonged prevention of light-induced retinal degeneration in DKO mice. Retinylamine nanoparticles hold promise for prolonged prophylactic treatment of human retinal degenerative diseases, including Stargardt disease and age-related macular degeneration. PMID:25617130

  14. Spatially coordinated kinase signaling regulates local axon degeneration.

    PubMed

    Chen, Mark; Maloney, Janice A; Kallop, Dara Y; Atwal, Jasvinder K; Tam, Stephen J; Baer, Kristin; Kissel, Holger; Kaminker, Joshua S; Lewcock, Joseph W; Weimer, Robby M; Watts, Ryan J

    2012-09-26

    In addition to being a hallmark of neurodegenerative disease, axon degeneration is used during development of the nervous system to prune unwanted connections. In development, axon degeneration is tightly regulated both temporally and spatially. Here, we provide evidence that degeneration cues are transduced through various kinase pathways functioning in spatially distinct compartments to regulate axon degeneration. Intriguingly, glycogen synthase kinase-3 (GSK3) acts centrally, likely modulating gene expression in the cell body to regulate distally restricted axon degeneration. Through a combination of genetic and pharmacological manipulations, including the generation of an analog-sensitive kinase allele mutant mouse for GSK3β, we show that the β isoform of GSK3, not the α isoform, is essential for developmental axon pruning in vitro and in vivo. Additionally, we identify the dleu2/mir15a/16-1 cluster, previously characterized as a regulator of B-cell proliferation, and the transcription factor tbx6, as likely downstream effectors of GSK3β in axon degeneration.

  15. X-linked recessive atrophic macular degeneration from RPGR mutation.

    PubMed

    Ayyagari, Radha; Demirci, F Yesim; Liu, Jiafan; Bingham, Eve L; Stringham, Heather; Kakuk, Laura E; Boehnke, Michael; Gorin, Michael B; Richards, Julia E; Sieving, Paul A

    2002-08-01

    We mapped a new X-linked recessive atrophic macular degeneration locus to Xp21.1-p11.4 and show allelic involvement of the gene RPGR, which normally causes severe peripheral retinal degeneration leading to global blindness. Ten affected males whom we examined had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration, emphasizing the dissociation of atrophic macular degeneration from generalized cone degenerations, including X-linked cone dystrophy (COD1). The RPGR gene nonsense mutation G-->T at open reading frame (ORF)15+1164 cosegregated with the disease and may create a donor splice site. Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies.

  16. Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation.

    PubMed

    Estacion, M; Vohra, B P S; Liu, S; Hoeijmakers, J; Faber, C G; Merkies, I S J; Lauria, G; Black, J A; Waxman, S G

    2015-09-01

    Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na(+) concentration ([Na(+)]) and intracellular [Ca(2+)] following stimulation with high [K(+)] compared with wild-type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca(2+)] transients evoked by high [K(+)] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K(+)] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K(+)] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca(2+) or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K(+)] and 2-DG. These results point to [Na(+)] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca(2+) toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy. PMID:26156380

  17. Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation

    PubMed Central

    Estacion, M.; Vohra, B. P. S; Liu, S.; Hoeijmakers, J.; Faber, C. G.; Merkies, I. S. J.; Lauria, G.; Black, J. A.

    2015-01-01

    Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na+ concentration ([Na+]) and intracellular [Ca2+] following stimulation with high [K+] compared with wild-type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca2+] transients evoked by high [K+] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K+] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K+] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca2+ or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K+] and 2-DG. These results point to [Na+] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca2+ toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy. PMID:26156380

  18. Acquired color vision loss and a possible mechanism of ganglion cell death in glaucoma.

    PubMed Central

    Nork, T M

    2000-01-01

    PURPOSE: First, to study the cellular mechanisms of acquired color vision loss in retinal detachment and diabetic retinopathy. Second, to learn why, in glaucoma, the type of color vision deficit that is observed is more characteristic of a retinal injury than it is of an optic neuropathy. Third, to test a hypothesis of photoreceptor-induced, ganglion cell death in glaucoma. METHODS: Various histologic techniques were employed to distinguish the L/M-cones (long/medium wavelength-sensitive cones, or red/green sensitive cones) from the S-cones (short wavelength-sensitive cones, or blue sensitive cones) in humans and monkeys with retinal detachment, humans with diabetic retinopathy, and both humans and monkeys with glaucoma. To test if the photoreceptors were contributing to ganglion cell death, laser photocoagulation was used in a experimental model of glaucoma to focally eliminate the photoreceptors. As a control, optic nerve transection was done following retinal laser photocoagulation in one animal. RESULTS: Selective and widespread loss of the S-cones was found in retinal detachment as well as diabetic retinopathy. By contrast, in human as well as experimental glaucoma, marked swelling of the L/M-cones was the predominant histopathologic feature. Retinal laser photocoagulation followed by experimental glaucoma resulted in selective protection of ganglion cells overlying the laser spots. This was not seen with retinal laser photocoagulation by optic nerve transection. CONCLUSIONS: In retinal detachment and diabetic retinopathy, acquired tritan-like color vision loss could be caused, or contributed to, by selective loss of the S-cones. Both L- and M-cones are affected in glaucoma, which is also consistent with a tritan-like deficit. Although not a therapeutic option, protection of ganglion cells by retinal laser in experimental glaucoma is consistent with an hypothesis of anterograde, photoreceptor-induced, ganglion cell death. Images FIGURE 1 FIGURE 2 FIGURE 3

  19. Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration.

    PubMed

    Karan, G; Lillo, C; Yang, Z; Cameron, D J; Locke, K G; Zhao, Y; Thirumalaichary, S; Li, C; Birch, D G; Vollmer-Snarr, H R; Williams, D S; Zhang, K

    2005-03-15

    Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness. PMID:15749821

  20. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the