“…1A) is clearly thinned, with vacuoles and no properly aligned morphological structures. This is in line with results from former experiments which demonstrated a significant thinning of the nerve after ONC but no difference between ONC/SHAM and ONC/rtACS 12 .Figure 1Histology of the intact and damaged optic nerve. In the photomicrographs provided in Fig.…”
Section: Resultssupporting
confidence: 90%
“…We confirmed results from our former work 12 by demonstrating the loss of visual evoked potentials (VEPs) in animals as early as day 4 post ONC, a time-point when virtually no cell death was found. There was no functional recovery on day 7 post lesion since the VEP peaks in both groups were not detectable as on day 4 (Fig.…”
Section: Resultssupporting
confidence: 90%
“…In addition, the usual early post-ONC swelling and late, pre-death shrinkage of RGCs were reduced by rtACS treatment 18 . However, in contrast to the successful restoration of function in chronic disease state, electrical stimulation applied immediately post-ONC did not induce functional improvement, as evaluated by behavioural brightness discrimination test and visual evoked potentials (VEPs) in rats 12, 17 .…”
Section: Introductionmentioning
confidence: 83%
“…After recovering from surgery and 10 days before crush a baseline ICON 32 was taken. The animals were then randomly assigned to one of the three groups: (i) ONC 78, 79 with subsequent rtACS (ONC/rtACS, n = 11) 12, 15 , (ii) ONC with sham stimulation (no current flow through electrode; ONC/SHAM, n = 8) and (iii) transient exposure of the optic nerve but no crush with sham rtACS (SHAM/SHAM, n = 9). The ONC and the first rtACS stimulation were done on day zero (experimental schedule, see Fig.…”
Repetitive transorbital alternating current stimulation (rtACS) improves vision in patients with chronic visual impairments and an acute treatment increased survival of retinal neurons after optic nerve crush (ONC) in rodent models of visual system injury. However, despite this protection no functional recovery could be detected in rats, which was interpreted as evidence of “silent survivor” cells. We now analysed the mechanisms underlying this “silent survival” effect. Using in vivo microscopy of the retina we investigated the survival and morphology of fluorescent neurons before and after ONC in animals receiving rtACS or sham treatment. One week after the crush, more neurons survived in the rtACS-treated group compared to sham-treated controls. In vivo imaging further revealed that in the initial post-ONC period, rtACS induced dendritic pruning in surviving neurons. In contrast, dendrites in untreated retinae degenerated slowly after the axonal trauma and neurons died. The complete loss of visual evoked potentials supports the hypothesis that cell signalling is abolished in the surviving neurons. Despite this evidence of “silencing”, intracellular free calcium imaging showed that the cells were still viable. We propose that early after trauma, complete dendritic stripping following rtACS protects neurons from excitotoxic cell death by silencing them.
“…1A) is clearly thinned, with vacuoles and no properly aligned morphological structures. This is in line with results from former experiments which demonstrated a significant thinning of the nerve after ONC but no difference between ONC/SHAM and ONC/rtACS 12 .Figure 1Histology of the intact and damaged optic nerve. In the photomicrographs provided in Fig.…”
Section: Resultssupporting
confidence: 90%
“…We confirmed results from our former work 12 by demonstrating the loss of visual evoked potentials (VEPs) in animals as early as day 4 post ONC, a time-point when virtually no cell death was found. There was no functional recovery on day 7 post lesion since the VEP peaks in both groups were not detectable as on day 4 (Fig.…”
Section: Resultssupporting
confidence: 90%
“…In addition, the usual early post-ONC swelling and late, pre-death shrinkage of RGCs were reduced by rtACS treatment 18 . However, in contrast to the successful restoration of function in chronic disease state, electrical stimulation applied immediately post-ONC did not induce functional improvement, as evaluated by behavioural brightness discrimination test and visual evoked potentials (VEPs) in rats 12, 17 .…”
Section: Introductionmentioning
confidence: 83%
“…After recovering from surgery and 10 days before crush a baseline ICON 32 was taken. The animals were then randomly assigned to one of the three groups: (i) ONC 78, 79 with subsequent rtACS (ONC/rtACS, n = 11) 12, 15 , (ii) ONC with sham stimulation (no current flow through electrode; ONC/SHAM, n = 8) and (iii) transient exposure of the optic nerve but no crush with sham rtACS (SHAM/SHAM, n = 9). The ONC and the first rtACS stimulation were done on day zero (experimental schedule, see Fig.…”
Repetitive transorbital alternating current stimulation (rtACS) improves vision in patients with chronic visual impairments and an acute treatment increased survival of retinal neurons after optic nerve crush (ONC) in rodent models of visual system injury. However, despite this protection no functional recovery could be detected in rats, which was interpreted as evidence of “silent survivor” cells. We now analysed the mechanisms underlying this “silent survival” effect. Using in vivo microscopy of the retina we investigated the survival and morphology of fluorescent neurons before and after ONC in animals receiving rtACS or sham treatment. One week after the crush, more neurons survived in the rtACS-treated group compared to sham-treated controls. In vivo imaging further revealed that in the initial post-ONC period, rtACS induced dendritic pruning in surviving neurons. In contrast, dendrites in untreated retinae degenerated slowly after the axonal trauma and neurons died. The complete loss of visual evoked potentials supports the hypothesis that cell signalling is abolished in the surviving neurons. Despite this evidence of “silencing”, intracellular free calcium imaging showed that the cells were still viable. We propose that early after trauma, complete dendritic stripping following rtACS protects neurons from excitotoxic cell death by silencing them.
“…TES also preserves ERG b-waves and scotopic threshold response (STR) in RCS rats (Morimoto et al, 2007). Finally, TES modulates brain oscillations in the visual cortex after deafferentation that occurs after optic nerve crush in rats (Sergeeva et al, 2012, 2015). …”
Low-level electrical stimulation to the eye has been shown to be neuroprotective against retinal degeneration in both human and animal subjects, using approaches such as subretinal implants and transcorneal electrical stimulation. In this study, we investigated the benefits of whole-eye electrical stimulation (WES) in a rodent model of retinitis pigmentosa. Transgenic rats with a P23H-1 rhodopsin mutation were treated with 30 min of low-level electrical stimulation (4 μA at 5 Hz; n = 10) or sham stimulation (Sham group; n = 15), twice per week, from 4 to 24 weeks of age. Retinal and visual functions were assessed every 4 weeks using electroretinography and optokinetic tracking, respectively. At the final time point, eyes were enucleated and processed for histology. Separate cohorts were stimulated once for 30 min, and retinal tissue harvested at 1 h and 24 h post-stimulation for real-time PCR detection of growth factors and inflammatory and apoptotic markers. At all time-points after treatment, WES-treated rat eyes exhibited significantly higher spatial frequency thresholds than untreated eyes. Inner retinal function, as measured by ERG oscillatory potentials (OPs), showed significantly improved OP amplitudes at 8 and 12 weeks post-WES compared to Sham eyes. Additionally, while photoreceptor segment and nuclei thicknesses in P23H-1 rats did not change between treatment groups, WES-treated eyes had significantly greater numbers of retinal ganglion cell nuclei than Sham eyes at 20 weeks post-WES. Gene expression levels of brain-derived neurotrophic factor (BDNF), caspase 3, fibroblast growth factor 2 (FGF2), and glutamine synthetase (GS) were significantly higher at 1 h, but not 24 h after WES treatment. Our findings suggest that WES has a beneficial effect on visual function in a rat model of retinal degeneration and that post-receptoral neurons may be particularly responsive to electrical stimulation therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
