Electrical stimulation ameliorates light-induced photoreceptor degeneration in vitro via suppressing the proinflammatory effect of microglia and enhancing the neurotrophic potential of Müller cells

Zhou, Wenting; Ni, Yushan; Jin, Zi‐Bing; Zhang, Meng; Wu, Jihong; Zhu, Ying; Xu, Gezhi; Gan, Dekang

doi:10.1016/j.expneurol.2012.08.029

Cited by 69 publications

(58 citation statements)

References 62 publications

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“…The American Journal of Pathology -ajp.amjpathol.org 58,59 In primary microglia isolated from retinas of SpragueDawley rats, the inhibitory effects of ES on the secretion of IL-1b and tumor necrosis factor-a were confirmed, as well as favorable effects on the production of brain-derived neurotrophic factor and ciliary nerve trophic factor in Müller cells 35 and the down-regulation of the proapoptopic gene Bax. 26 Willmann et al 34 also showed that TES led to clear changes in the expression of neuroprotective genes and that different genes may be expressed, depending on whether TES was applied to a healthy or diseased retina.…”

Section: Improving Vision By Electrostimulationmentioning

confidence: 88%

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Electrical Stimulation as a Means for Improving Vision

Sehic

Guo

Cho

et al. 2016

The American Journal of Pathology

138

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Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision. (Am J Pathol 2016 http://dx

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Section: Improving Vision By Electrostimulationmentioning

confidence: 88%

“…15e35 These studies can be categorized as follows: i) healthy animals 17e19, 23,26,31,34 ; ii) transgenic animals 22,28 ; iii) animals as a disease model for RP 21 ; iv) animals with induced ischemic insult, 27,29,33 optic nerve crush, 15,16,20,32 and transected optic nerve 24,25 ; and v) animal cells isolated from the retina. 35 …”

Section: Animal Experimentsmentioning

confidence: 99%

Electrical Stimulation as a Means for Improving Vision

Sehic

Guo

Cho

et al. 2016

The American Journal of Pathology

138

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“…[15][16][17][18] Several pioneering studies sought to clarify the functional mechanisms underlying TES-induced neuroprotective effects, showing that the beneficial effects are not attributed to a single pathway. [19][20] Conversely, multiple mechanisms collectively promote cell survival and contribute to cellular homeostasis of the TES-treated retina. For example, TES simultaneously regulates the expression of apoptosis-associated genes and neurotrophic factors to neutralize the intrinsic survival microenvironment of light-damaged retinas.…”

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confidence: 99%

“…15 Meanwhile, TES-induced anti-inflammatory effects are also correlated with this amelioration process. 20 The membranes of retinal neurons, such as photoreceptors, retinal ganglion cells (RGCs), and Müller cells, are rich in voltage-gated ion channels, which are reactive to extracellular electric field changes. 21,22 Transcorneal electrical stimulation can change the functional status of these retinal neurons by altering the activity of transmembrane voltagegated ion channels.…”

mentioning

confidence: 99%

Topographic Quantification of the Transcorneal Electrical Stimulation (TES)–Induced Protective Effects on N-Methyl-N-Nitrosourea–Treated Retinas

Tao

Chen

Liu

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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METHODS. N-methyl-N-nitrosourea-administered mice received TES or sham stimulations and were subsequently subjected to electroretinography (ERG), multielectrode array (MEA), and histologic and immunohistochemistry examinations. Quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) analyses were also performed to determine the mRNA levels of Bax, Bcl-2, Calpain-2, Caspase-3, brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF). RESULTS.Amplitudes of ERG b-wave in the TES-treated mice were significantly larger than those in the sham controls (P < 0.01). Microelectrode array examination revealed that the photoreceptors in TES-treated retina were efficiently preserved (P < 0.01). Morphologic measurements showed that the central retina region was more consolidated than the other areas in the TES-treated mice. Together with the disproportionate distribution of immunostaining in retinal flat mounts, these findings indicated that different rescuing kinetics existed among regional photoreceptors. Compared with the sham controls, a significantly increased signal-to-noise ratio was also found in the TES-treated mice (TES100: 2.02 6 1.12; TES200: 4.42 6 1.51; sham: 0.25 6 0.13; P < 0.01). Moreover, qRT-PCR measurements suggested that the altered expression of several apoptotic factors and neurotrophic cytokines was correlated with TES-induced protection.CONCLUSIONS. Regional photoreceptors in the MNU-administered retinas exhibit different sensitivities to TES. Transcorneal electrical stimulation is capable of ameliorating MNUinduced photoreceptor degeneration and rectifying abnormalities in the inner visual signal pathways.Keywords: transcorneal electrical stimulation, therapeutic strategy, retinitis pigmentosa R etinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by initially impaired dark-adapted sight, progressive deterioration of visual fields, and eventual blindness. 1,2 Currently, the pathologic mechanisms of RP remain poorly understood, and there is no satisfactory therapeutic intervention.3 Retinitis pigmentosa models can be used to explore the pathologic mechanisms underlying this disorder, providing insights into the development of effective therapeutics. The N-methyl-N-nitrosourea (MNU) can pharmacologically induce photoreceptor degeneration. After a single systemic administration, active signs of retinal degeneration, such as decreased outer nuclear layer (ONL) thickness, degraded electroretinogram (ERG) response, and hyperexpressed apoptotic labeling, are indistinct in the MNU-treated retinas due to the selective photoreceptor cell loss. The mechanism underlying MNU-induced photoreceptor death is the principal alkylation of DNA, depending on the action of alkyladenine DNA glycosylase (Aag), an enzyme that removes alkylated bases via cleavage of glycosyl bond connecting base to the sugar phosphate backbone, thus generating abasic sites that can be further processed by the base excision repair machinery.4 N-methyl-N-nitrosourea ...

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“…L-type calcium channels may control the release of these growth factors, as shown by using nifedipine, an L-type voltage dependent calcium channel blocker, to suppress the upregulation of IGF-1 and BDNF [21,22]. In addition, EST downregulates proinflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor (TNF)-alpha [24] and the pro-apoptotic gene Bax [16]. Finally, gene expression analysis of wild-type retina following 1 h of TES showed downregulation of Bax and differential expression of the TNF family [25].…”

Section: Mechanisms Underlying the Neuroprotective Effects Of Estmentioning

confidence: 99%

Neuroprotective Effects of Low Level Electrical Stimulation Therapy on Retinal Degeneration

Pardue

Ciavatta

Hetling

2014

Retinal Degenerative Diseases

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Low-level electrical stimulation applied to the eye has been shown to have neuroprotective effects on photoreceptors and retinal ganglion cells. In this review, we compare the effects of Subretinal Electrical Stimulation (SES), Transcorneal Electrical Stimulation (TES), and Whole Eye Stimulation (WES) on preserving retinal structure and function, and visual acuity, in retinal degeneration. Similarities and differences in stimulus parameters, targeted cells and growth factor expression will be discussed with emphasis on studies that have translated laboratory findings into clinical trials.

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Electrical stimulation ameliorates light-induced photoreceptor degeneration in vitro via suppressing the proinflammatory effect of microglia and enhancing the neurotrophic potential of Müller cells

Cited by 69 publications

References 62 publications

Electrical Stimulation as a Means for Improving Vision

Electrical Stimulation as a Means for Improving Vision

Topographic Quantification of the Transcorneal Electrical Stimulation (TES)–Induced Protective Effects on N-Methyl-N-Nitrosourea–Treated Retinas

Neuroprotective Effects of Low Level Electrical Stimulation Therapy on Retinal Degeneration

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