摘要
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 electrica
基金
supported by The Norwegian Research Council
Department of Ophthalmology,Oslo University Hospital,Oslo,Norway(to TPU)
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).
