Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on pho...Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.展开更多
Background: Up to one in three patients implanted with a cardiac resynchronization therapy-defibrillator (CRT-D) device experience phrenic nerve stimulation (PNS). Quadripolar leads are effective at reducing PNS, but ...Background: Up to one in three patients implanted with a cardiac resynchronization therapy-defibrillator (CRT-D) device experience phrenic nerve stimulation (PNS). Quadripolar leads are effective at reducing PNS, but compared to standard bipolar leads they have limitations related to maneuverability and high pacing thresholds. The ability of standard bipolar leads to overcome PNS is explored here. Methods: The French multicenter, observational study ORPHEE enrolled 90 CRT-D-eligible patients. Detection of PNS took place after satisfactory positioning of the LV bipolar lead (stable pacing threshold - LV ring, LV tip - RV ring and LV ring - RV coil) could prevent PNS from occurring in at least 90% of patients. Results: In 80 evaluable patients, PNS was reported in 12 patients (15%). Reprogramming overcame PNS in 10 patients: LV ring - RV coil in 8 patients;LV tip - LV ring in 1;and LV tip- RV ring in 1. As PNS was avoided in 78 of 80 patients (97.5%), the primary endpoint was significant (97.5% vs. 90%, p = 0.01). Conclusion: During CRT-D implantation, PNS occurred in 15% of patients. In most (97.5%) implanted patients, PNS could be avoided by vector reprogramming using a bipolar LV lead. For patients whose coronary sinus anatomy precludes the implantation of multi-electrode leads, bipolar leads are a suitable, reliable alternative.展开更多
Objective:bipolar cells(BCs)communicate with amacrine and ganglion cells of the retina via both transient and sustained neurotransmitter release in ribbon synapses.Reconstructing the published quantitative release dat...Objective:bipolar cells(BCs)communicate with amacrine and ganglion cells of the retina via both transient and sustained neurotransmitter release in ribbon synapses.Reconstructing the published quantitative release data from electrical soma stimulation(voltage clamp experiments)of rat rod BCs were used to develop two simple models to predict the number of released vesicles as time series.In the experiment,the currents coming to the All amacrine cell originating from releasing vesicles from the rod BC were recorded using paired-recordings in whole-cell voltage-clamp method.Method:one of the models is based directly on terminal transmembrane voltage,so-called ‘model’,whereas the temporally exacter modelCa includes changes of intracellular calcium concentrations at terminals.Result:the intracellular calcium concentration method replicates a 0.43 ms signal delay for the transient release to pulsatile stimulation as a consequence of calcium channel dynamics in the presynaptic membrane,while the modelV has no signal delay.Both models produce the quite similar results in low stimuli amplitudes.However,for large stimulation intensities that may be done during extracellular stimulations in retinal implants,the modelCa predicts that the reversal potential of calcium limits the number of transiently released vesicles.Adding sodium and potassium ion channels to the axon of the cell enable to study the impact of spikes on the transient release in BC ribbons.Conclusion:a spike elicited by somatic stimulation causes the rapid release of all vesicles that are available for transient release,while a non-spiking BC with a similar morphometry needs stronger stimuli for any transient vesicle release.During extracellular stimulation,there was almost no difference in transient release between the active and passive cells because in both cases the terminal membrane of the cell senses the same potentials originating from the microelectrode.An exception was found for long pulses when the spike has the possibility to generate a higher terminal voltage than the passive cell.Simulated periodic 5 Hz stimulation showed a reduced transient release of 3 vesicles per stimulus,which is a recovery effect.展开更多
The centrifugal innervation of the retina has been extensively described in birds, in which retinal centrifugal fibres originating in the nucleus isthmoopticus terminate directly on amacrine cells. Physiological role ...The centrifugal innervation of the retina has been extensively described in birds, in which retinal centrifugal fibres originating in the nucleus isthmoopticus terminate directly on amacrine cells. Physiological role of these fibres has been shown to cause an increase in responsiveness of most ganglion cells, which is probably caused by suppression of the inhibitory surround of the cell receptive fields provided by amacrine cells. Recently,展开更多
目的探讨右侧前额叶皮质重复经颅磁刺激(r TMS)治疗双相障碍躁狂发作的疗效和安全性。方法 64例双相障碍躁狂发作患者随机分为研究组32例和对照组32例,两组均给予碳酸锂缓释片;研究组给予20Hz r TMS真刺激,对照组给予伪刺激,每天1次,共1...目的探讨右侧前额叶皮质重复经颅磁刺激(r TMS)治疗双相障碍躁狂发作的疗效和安全性。方法 64例双相障碍躁狂发作患者随机分为研究组32例和对照组32例,两组均给予碳酸锂缓释片;研究组给予20Hz r TMS真刺激,对照组给予伪刺激,每天1次,共14次。采用躁狂量表(BRMS)、治疗中出现的症状量表(TESS)于治疗前和治疗后7、14d分别评估临床疗效及不良反应。结果两组治疗前及治疗后7d,BRMS评分两组差异无统计学意义(P>0.05);治疗后14d,研究组BRMS评分明显低于对照组,差异有统计学意义(P<0.05);至治疗结束研究组有效率明显高于对照组,差异有统计学意义(P<0.05),未观察到明显不良反应。结论心境稳定剂合并右前额皮质r TMS治疗双相障碍躁狂发作患者有效、安全。展开更多
基金supported by The Norwegian Research CouncilDepartment of Ophthalmology,Oslo University Hospital,Oslo,Norway(to TPU)+10 种基金Department of Medical Biochemistry,Oslo University Hospital,Oslo,Norway(to TPU)The Norwegian Association for the Blind and Partially Sighted(to TPU)The Ministry of Science and Technology of Taiwan,China MOST 105-2917-I-002-031,MOST 109-2917-I-564-032(to KC)The Scientific and Technological Research Council of Turkiye-TUBITAK(to KG)BrightFocus Foundation(to KSC)the Massachusetts Lions Foundation(to KSC)National Eye Institute Grant EY031696(to DFC)Harvard NeuroDiscovery Center Grant(to DFC)Department of Defense(USA)HT9425-23-1-1045(to DFC and AL)Core Grant for Vision Research from NIH/NEI to the Schepens Eye Research Institute(P30EY003790)South-Eastern Norway Regional Health Authority and the Norwegian Society of the Blind(to TPU).
文摘Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.
文摘Background: Up to one in three patients implanted with a cardiac resynchronization therapy-defibrillator (CRT-D) device experience phrenic nerve stimulation (PNS). Quadripolar leads are effective at reducing PNS, but compared to standard bipolar leads they have limitations related to maneuverability and high pacing thresholds. The ability of standard bipolar leads to overcome PNS is explored here. Methods: The French multicenter, observational study ORPHEE enrolled 90 CRT-D-eligible patients. Detection of PNS took place after satisfactory positioning of the LV bipolar lead (stable pacing threshold - LV ring, LV tip - RV ring and LV ring - RV coil) could prevent PNS from occurring in at least 90% of patients. Results: In 80 evaluable patients, PNS was reported in 12 patients (15%). Reprogramming overcame PNS in 10 patients: LV ring - RV coil in 8 patients;LV tip - LV ring in 1;and LV tip- RV ring in 1. As PNS was avoided in 78 of 80 patients (97.5%), the primary endpoint was significant (97.5% vs. 90%, p = 0.01). Conclusion: During CRT-D implantation, PNS occurred in 15% of patients. In most (97.5%) implanted patients, PNS could be avoided by vector reprogramming using a bipolar LV lead. For patients whose coronary sinus anatomy precludes the implantation of multi-electrode leads, bipolar leads are a suitable, reliable alternative.
基金HB was supported by the European Institute of Innovation and Technology Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 674901(switchboard).
文摘Objective:bipolar cells(BCs)communicate with amacrine and ganglion cells of the retina via both transient and sustained neurotransmitter release in ribbon synapses.Reconstructing the published quantitative release data from electrical soma stimulation(voltage clamp experiments)of rat rod BCs were used to develop two simple models to predict the number of released vesicles as time series.In the experiment,the currents coming to the All amacrine cell originating from releasing vesicles from the rod BC were recorded using paired-recordings in whole-cell voltage-clamp method.Method:one of the models is based directly on terminal transmembrane voltage,so-called ‘model’,whereas the temporally exacter modelCa includes changes of intracellular calcium concentrations at terminals.Result:the intracellular calcium concentration method replicates a 0.43 ms signal delay for the transient release to pulsatile stimulation as a consequence of calcium channel dynamics in the presynaptic membrane,while the modelV has no signal delay.Both models produce the quite similar results in low stimuli amplitudes.However,for large stimulation intensities that may be done during extracellular stimulations in retinal implants,the modelCa predicts that the reversal potential of calcium limits the number of transiently released vesicles.Adding sodium and potassium ion channels to the axon of the cell enable to study the impact of spikes on the transient release in BC ribbons.Conclusion:a spike elicited by somatic stimulation causes the rapid release of all vesicles that are available for transient release,while a non-spiking BC with a similar morphometry needs stronger stimuli for any transient vesicle release.During extracellular stimulation,there was almost no difference in transient release between the active and passive cells because in both cases the terminal membrane of the cell senses the same potentials originating from the microelectrode.An exception was found for long pulses when the spike has the possibility to generate a higher terminal voltage than the passive cell.Simulated periodic 5 Hz stimulation showed a reduced transient release of 3 vesicles per stimulus,which is a recovery effect.
基金Project supported by grants from the State Commission of ScienceTechnology of China+1 种基金National Institutes of Health of USAthe International Human Frontier Science Program (HFSP)
文摘The centrifugal innervation of the retina has been extensively described in birds, in which retinal centrifugal fibres originating in the nucleus isthmoopticus terminate directly on amacrine cells. Physiological role of these fibres has been shown to cause an increase in responsiveness of most ganglion cells, which is probably caused by suppression of the inhibitory surround of the cell receptive fields provided by amacrine cells. Recently,
