Randomized controlled trial of electro‐stimulation therapies to modulate retinal blood flow and visual function in retinitis pigmentosa

Bittner, Ava K; Seger, Kenneth R.; Salveson, Rachel M; Kayser, Sarah; Morrison, Natalia; Vargas, Patricia; Mendelsohn, Deborah; Han, Jorge; Bai, Hua; Dagnelie, Gislin; Benavente, Alexandra; Ramella‐Roman, Jessica C.

doi:10.1111/aos.13581

Cited by 42 publications

(46 citation statements)

References 44 publications

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“…The present findings offer the foundation for clinical observations that ES treatment may have the potential to improve sight in patients with photoreceptor degeneration. 6,12,35 Our data agree with earlier findings that ES enhanced ERG b-wave and ONL thickness or photoreceptor survival. 7,36 Moreover, our results suggest that ES drove molecular changes in MCs toward a progenitor-like status.…”

Section: Discussionsupporting

confidence: 92%

“…7,8 The protective effects of minimal or noninvasive ES have since been reported in patients with AMD, RP, and retinal artery occlusion. 6,[9][10][11][12][13]14 Importantly, no significant safety-related adverse effects were observed in any of these studies; however, due to the lack of standardization of ES parameters in clinical trials and animal studies, the effects of ES have often been inconsistent or even controversial. 15 To date, it is not yet known why or how ES improves vision.…”

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confidence: 99%

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Noninvasive Electrical Stimulation Improves Photoreceptor Survival and Retinal Function in Mice with Inherited Photoreceptor Degeneration

Enayati

Chang

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Neurons carry electrical signals and communicate via electrical activities. The therapeutic potential of electrical stimulation (ES) for the nervous system, including the retina, through improvement of cell survival and function has been noted. Here we investigated the neuroprotective and regenerative potential of ES in a mouse model of inherited retinal degeneration. METHODS. Rhodopsin-deficient (Rho −/−) mice received one or two sessions of transpalpebral ES or sham treatments for 7 consecutive days. Intraperitoneal injection of 5-ethynyl-2-deoxyuridine was used to label proliferating cells. Weekly electroretinograms were performed to monitor retinal function. Retinal morphology, photoreceptor survival, and regeneration were evaluated in vivo using immunohistochemistry and genetic fatemapping techniques. Müller cell (MC) cultures were employed to further define the optimal conditions of ES application. RESULTS. Noninvasive transpalpebral ES in Rho −/− mice improved photoreceptor survival and electroretinography function in vivo. ES also triggered residential retinal progenitorlike cells such as MCs to reenter the cell cycle, possibly producing new photoreceptors, as shown by immunohistochemistry and genetic fate-mapping techniques. ES directly stimulated cell proliferation and the expression of progenitor cell markers in MC cultures, at least partially through bFGF signaling. CONCLUSIONS. Our study showed that transpalpebral ES improved photoreceptor survival and retinal function and induced the proliferation, probably photoreceptor regeneration, of MCs; this occurs via stimulation of the bFGF pathways. These results suggest the exciting possibility of applying noninvasive ES as a versatile tool for preventing photoreceptor loss and mobilizing endogenous progenitors for reversing vision loss in patients with photoreceptor degeneration.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Noninvasive Electrical Stimulation Improves Photoreceptor Survival and Retinal Function in Mice with Inherited Photoreceptor Degeneration

Enayati

Chang

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…This alternating microcurrent stimulation is suggested to act via several mechanisms: neurotrophic, anti-apoptotic, anti-glutammatic, and anti-inflammatory (Sehic et al, 2016). For this reason, tcES is used to treat nonarteritic ischemic optic neuropathy (NAION) (Fujikado et al, 2006), retinal artery occlusion (RAO) (Inomata et al, 2007;Oono et al, 2011;Naycheva et al, 2013), traumatic optic neuropathy (TON) (Fujikado et al, 2006), retinitis pigmentosa (Schatz et al, 2011(Schatz et al, , 2017Robles-Camarillo et al, 2013;Bittner et al, 2018aBittner et al, , 2018b, and macular dystrophy (Ozeki et al, 2013). We examined 11 papers on tcES.…”

Section: Study Identification and Quality Assessmentmentioning

confidence: 99%

Non-invasive current stimulation in vision recovery: a review of the literature

Perin

Viganò

Piscitelli

et al. 2019

Restorative Neurology and Neuroscience

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Background: Around 253 million people worldwide suffer from irreversible visual damage. Numerous studies have been carried out in order to unveil the effects of electrical stimulation (ES) as a useful tool for rehabilitation for different visual conditions and pathologies. Objective: This systematic review aimed to 1) examine the current evidence of ES efficacy for the treatment of visual pathologies and 2) define the corresponding degree of the recommendation of different ES techniques. Methods: A systematic review was conducted in MEDLINE and Cochrane Library database to collect documents published between 2000 and 2018. For each study, Level of Evidence of Effectiveness of ES as well as the Class of Quality for the treatment of different visual pathologies were determined. Results: Thirty-eight articles were included. Studies were grouped according to the pathology treated and the type of stimulation administered. The first group included studies treating pre-chiasmatic pathologies (age-related macular degeneration, macular dystrophy, retinal artery occlusion, retinitis pigmentosa, glaucoma, optic nerve damage, and optic neuropathy) using pre-chiasmatic stimulation; the second group included studies treating both pre-chiasmatic pathologies (amblyopia, myopia) and post-chiasmatic pathologies or brain conditions (hemianopsia, brain trauma) by means of post-chiasmatic stimulation. In the first group, repetitive transorbital alternating current stimulation (rtACS) reached level A recommendation, and transcorneal electrical stimulation (tcES) reached level B. In the second group, both high-frequency random noise stimulation (hf-RNS) and transcranial direct current stimulation (tDCS) reached level C recommendation. Conclusions: Study's findings suggest conclusive evidence for rtACS treatment. For other protocols results are promising but not conclusive since the examined studies assessed different stimulation parameters and endpoints. A comparison of the effects of different combinations of these variables still lacks in the literature. Further studies are needed to optimize existing protocols and determine if different protocols are needed for different diseases.

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“…Sham controls are documented to be widely used in basic and clinical research ( Naycheva et al, 2013 ; Bola et al, 2014 ; Zheng et al, 2017 ). Moreover, a good number of studies in retinal electrical stimulation genre including preclinical studies on rodents and clinical studies have also employed the use of sham controls ( Henrich-Noack et al, 2013 ; Sehic et al, 2016 ; Bittner et al, 2017 ; Schatz et al, 2017 ). Furthermore, we have used only rd10 mice as opposed to the wild type C57BL/6 mice because we wanted to ensure uniformity in the mice genotype for comparison of our ECoG results and to avoid unexpected ECoG results with wild type mice which for instance could possibly arise from genotype, or asymptomatic eye damage during animal housing or from other circumstances which could go unnoticed thus leading to false negative ECoG results.…”

Section: Discussionmentioning

confidence: 99%

Excitation of the Pre-frontal and Primary Visual Cortex in Response to Transcorneal Electrical Stimulation in Retinal Degeneration Mice

Agadagba

Chan

2020

Front. Neurosci.

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Retinal degeneration (rd) is one of the leading causes of blindness in the modern world today. Various strategies including electrical stimulation are being researched for the restoration of partial or complete vision. Previous studies have demonstrated that the effectiveness of electrical stimulation in somatosensory, frontal and visual cortices is dependent on stimulation parameters including stimulation frequency and brain states. The aim of the study is to investigate the effect of applying a prolonged electrical stimulation on the eye of rd mice with various stimulation frequencies, in awake and anesthetized brain states. We recorded spontaneous electrocorticogram (ECoG) neural activity in prefrontal cortex and primary visual cortex in a mouse model of retinitis pigmentosa (RP) after prolonged (5-day) transcorneal electrical stimulation (pTES) at various frequencies (2, 10, and 20 Hz). We evaluated the absolute power and coherence of spontaneous ECoG neural activities in contralateral primary visual cortex (contra Vcx) and contralateral pre-frontal cortex (contra PFx). Under the awake state, the absolute power of theta, alpha and beta oscillations in contra Vcx, at 10 Hz stimulation, was higher than in the sham group. Under the anesthetized state, the absolute power of medium-, high-, and ultra-high gamma oscillations in the contra PFx, at 2 Hz stimulation, was higher than in the sham group. We also observed that the ultra-high gamma band coherence in contra Vcx-contra PFx was higher than in the sham group, with both 10 and 20 Hz stimulation frequencies. Our results showed that pTES modulates rd brain oscillations in a frequency and brain state-dependent manner. These findings suggest that non-invasive electrical stimulation of retina changes patterns of neural oscillations in the brain circuitry. This also provides a starting point for investigating the sustained effect of electrical stimulation of the retina to brain activities.

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Randomized controlled trial of electro‐stimulation therapies to modulate retinal blood flow and visual function in retinitis pigmentosa

Abstract: Increased blood flow following electro-stimulation therapies is an objective, physiological change that occurred in addition to visual function improvements in some RP patients.

Cited by 42 publications

References 44 publications

Noninvasive Electrical Stimulation Improves Photoreceptor Survival and Retinal Function in Mice with Inherited Photoreceptor Degeneration

Noninvasive Electrical Stimulation Improves Photoreceptor Survival and Retinal Function in Mice with Inherited Photoreceptor Degeneration

Non-invasive current stimulation in vision recovery: a review of the literature

Excitation of the Pre-frontal and Primary Visual Cortex in Response to Transcorneal Electrical Stimulation in Retinal Degeneration Mice

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