Neuroprotective Effects of Low Level Electrical Stimulation Therapy on Retinal Degeneration

Pardue, Machelle T.; Ciavatta, Vincent T.; Hetling, John R.

doi:10.1007/978-1-4614-3209-8_106

Cited by 14 publications

(20 citation statements)

References 26 publications

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“…Single-session and repeated treatments of tDCS have been found to enhance cognitive and motor functions and ameliorate psychiatric disorders, such as depression, substance abuse, schizophrenia, and binge eating disorder 2–7. In retina, transcorneal electrical stimulation has been reported to affect ganglion cell survival and axonal growth8,9 and to preserve retinal function in a number of retinal degeneration models 10–13…”

Section: Introductionmentioning

confidence: 99%

Effects of tDCS-like electrical stimulation on retinal ganglion cells

Strang

Ray

Boggiano

et al. 2018

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PurposeTranscranial direct current stimulation (tDCS) has been studied in humans for its effects on enhancement of learning, amelioration of psychiatric disorders, and modification of other behaviors for over 50 years. Typical treatments involve injecting 2 mA current through scalp electrodes for 20 minutes, sometimes repeated weekly for two to five sessions. Little is known about the direct effects of tDCS at the neural circuit or the cellular level. This study assessed the effects of tDCS-like currents on the central nervous system by recording effects on retinal ganglion cell responsiveness using the rabbit retina eyecup preparation.Materials and methodsWe examined changes in firing to On and Off light stimuli during and after brief applications of a range of currents and polarity and in different classes of ganglion cells.ResultsThe responses of Sustained cells were consistently suppressed during the first round of current application, but responses could be enhanced after subsequent rounds of stimulation. The observed first round suppression was independent of current polarity, amplitude, or number of trials. However, the light responses of Transient cells were more likely to be enhanced by negative currents and unaffected or suppressed by first round positive currents. Short-duration currents, that is, minutes, as low as 2.5 µA produced a remarkable persistency of firing changes, for up to 1.5 hours, after cessation of current.ConclusionThe results are consistent with postulated tDCS alteration of central nervous system function, which outlast the tDCS session and provide evidence for the isolated retina as a useful model to understand tDCS actions at the neuronal level.

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Section: Introductionmentioning

confidence: 99%

Effects of tDCS-like electrical stimulation on retinal ganglion cells

Strang

Ray

Boggiano

et al. 2018

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“…In choosing the WES current level for the current study, we consider the fact that larger protective effects of retinal function had been found for SES than WES. Thus, for this study we chose a 4 μA current, nearly 3 times larger than the 1.5 μA used in the Rahami et al study, but much lower than the current used for SES and TES which ranges from 100 to 900 μA (Pardue et al, 2014). Thus, our inability to replicate the preserved b-wave and rod sensitivity found in Rahami et al may be due to the higher current levels.…”

Section: Discussionmentioning

confidence: 99%

“…However, in this manuscript, we describe TES as delivery of stimulation to the eye when both the active and reference electrodes are both located on the ocular globe, such as with a bipolar contact lens electrode in human subjects (Fujikado et al, 2006; Inomata et al, 2007; Oono et al, 2011). In this way, electrical field and current are focused primarily in the anterior segment of the eye, rather than the inner retina as in SES (Pardue et al, 2014). Like TES, WES places an active electrode on the cornea, but the reference electrode is placed in the mouth or elsewhere on the head, permitting the current to become more uniformly distributed throughout the eye (Rahmani et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…This approach has often been referred to as TES in the literature and can be applied with a DTL electrode in animals and humans (Schatz et al, 2011, 2012) or contact lens in animal models (Willmann et al, 2011; Wrobel et al, 2011). Current magnitudes for TES and WES treatments range from 1.5 to 1000 μA (Pardue et al, 2014). Another EST approach is transorbital stimulation in which the electrodes are applied around the ocular orbit, but not directly on the eye in humans (Gall et al, 2011, 2015; Sabel et al, 2011; Schmidt et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats

Hanif

Kim

Thomas

et al. 2016

Experimental Eye Research

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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.

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“…A surprising byproduct of prosthetic research was the discovery that electrical stimulation of the retina, even below levels necessary to elicit phosphenes may have neurotrophic effect and slow the progression of retinal degeneration (Morimoto et al, 2007;Pardue, Ciavatta, & Hetling, 2014;Schatz et al, 2011). It may therefore prove beneficial to implant retinal prostheses earlier to not only replace the vision that eventually will be lost, but to also delay retinal degeneration outside the implanted area.…”

Section: Do Implants Slow Degeneration?mentioning

confidence: 99%

Chapter 1 - Restoring Vision to the Blind: The New Age of Implanted Visual Prostheses

2014

Trans. Vis. Sci. Tech.

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Of the many devices investigated, retina-based devices have shown the greatest success. These devices are limited, however, to eye diseases that destroy the photoreceptors but leave, at the very least, the ganglion cells intact for direct stimulation (Kellner, 2000). Of those diseases, retinitis pigmentosa (RP) has been the most attractive candidate because some affected individuals reach near-complete blindness at a relatively early age, and the inner (neural) retina is relatively spared. In comparison, age-related macular degeneration (AMD) has a late onset and does not cause total blindness for many years, typically leaving the retinal periphery functional. At present, there are seven major ongoing retinal prosthesis projects that have either implanted test subjects or have concrete plans to do so in the near future. The Argus II developed by Second Sight (Second Sight Medical Products, Lausanne, Switzerland) has been implanted during clinical trials in over 30 patients in both Europe and the United States (Humayun et al., 2012) where it has also been approved for commercial sale (in 2011 and 2013, respectively [Rizzo et al., 2014]). Currently, approximately 45 commercial devices have been implanted. In comparison, the Alpha-IMS system of Retina Implant AG has been implanted during clinical trials in over 40 patients (Zrenner, 2013) and in 2013 received CE (Conformité Européenne) approval for commercial sale in the European Union with the first sales expected in 2014 (W. Wrobel, personal communication,). In addition to these two commercial devices, the IRIS device developed by Intelligent Medical Implants (IMI) was implanted in 20 patients in 2003 and 2004 (Hornig et al., 2007). This IMI (Innovative Medicines Initiative) device has been acquired by Pixium, which is conducting renewed clinical trials. Furthermore, devices developed by the Bionic Vision Australia consortium (Saunders et al., 2014) the Boston Retina Implant Project (Rizzo, 2011), Nidek Co., Ltd. (Nidek Co., Aichi, Japan) (Fujikado et al., 2011), and the Stanford-based photovoltaic retinal prosthesis (PRIMA) (Mandel et al., 2013; Mathieson et al., 2012) have announced plans to enter clinical trials in the next few years. Functional results from some of these retinal implants will be discussed below. Recent Advances in Optic Nerve and Thalamic Stimulation Optic nerve stimulation seeks to create action potentials in the axons of the ganglion cells. Whereas epiretinal stimulation targets these ganglion cells at or very near their cell bodies in order to preserve retinotopy (Fried, Lasker,

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Neuroprotective Effects of Low Level Electrical Stimulation Therapy on Retinal Degeneration

Cited by 14 publications

References 26 publications

Effects of tDCS-like electrical stimulation on retinal ganglion cells

Effects of tDCS-like electrical stimulation on retinal ganglion cells

Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats

Chapter 1 - Restoring Vision to the Blind: The New Age of Implanted Visual Prostheses

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