Optogenetic termination of atrial fibrillation in mice

Bruegmann, Tobias; Beiert, Thomas; Vogt, Christoph; Schrickel, Jan W.; Sasse, Philipp

doi:10.1093/cvr/cvx250

Cited by 64 publications

(67 citation statements)

References 46 publications

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“…We expect this technology will be a powerful tool in cardiac research because it allows for mechanistic dissection of the interplay between genotype and phenotype during normal and pathological cardiac physiology, as well as providing therapeutic interventions for cardiac arrhythmias. [ 9,60,61 ] In addition, this multifunctional platform could be easily translated to neuroscience applications, such as miniaturized implantable optoelectronic neural interfaces for bidirectional monitoring and modulating neural activity, [ 62,63 ] brain–machine interfaces, [ 64,65 ] closed‐loop therapeutic deep brain stimulation, [ 66,67 ] etc. Ongoing and future research will focus on developing scale‐up fabrication strategies, [ 68 ] high‐performance nanogrid electrodes with subcellular resolution to enable recordings from single cells, and large‐scale multisite implantable arrays for chronic in vivo cardiac, neural, and skeletal muscle optical interventions with electrophysiological recordings.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional Flexible Biointerfaces for Simultaneous Colocalized Optophysiology and Electrophysiology

Obaid

Yin

Tian

et al. 2020

Adv Funct Materials

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Recent developments in optophysiology techniques such as optogenetics have revolutionized the ability to actuate cell activity. Further combining optophysiology and electrophysiology will integrate the advantages from both optical and electrical modalities and yield enabling technologies that allow simultaneous monitoring of cellular activity in response to modulation, which are crucial for biomedical applications. However, multifunctional devices that can deliver optical stimuli to regions beneath the electrodes and perform simultaneous sensing remain largely unexplored. Existing transparent microelectrode technologies depend on external bulk optical instruments for optical interventions. Here, innovative monolithic integrated multifunctional microsystems are demonstrated by applying transparent nanogrid electrodes onto microscale light sources to permit simultaneous electrophysiology and optical modulation at the same anatomical site. The nanogrid electrodes have transmittances > 70% with a low normalized impedance of 5.9 Ω cm2. Additional features of the devices include superior mechanical flexibility, minimized light‐induced electrical artifacts, and excellent biocompatibility. Ex vivo experiments demonstrate that the multifunctional devices can record abnormal heart rhythm in transgenic mouse hearts and simultaneously restore the sinus rhythm via optogenetic pacing. This work provides a versatile approach for constructing multifunctional colocalized biointerfaces containing crosstalk‐free optical and electrical modalities with expanded opportunities in both fundamental and applied biomedical research.

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Section: Resultsmentioning

confidence: 99%

Multifunctional Flexible Biointerfaces for Simultaneous Colocalized Optophysiology and Electrophysiology

Obaid

Yin

Tian

et al. 2020

Adv Funct Materials

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“…The AADwc method can provide an efficient and optimal strategy in the design of control schemes for the removal of any type of anchored reentry in the heart, as it clearly demonstrates that real-time spatiotemporal control of scroll waves can be achieved, even with sub-transmural illumination of cardiac tissue. Although in practice, the application of optogenetics to cardiology, is, in itself, a debatable topic, recent advances in cardiac optogenetics [46][47][48][49][50][51][52] promise a brighter future. One of the biggest challenges faced by existing scroll wave control methods is that the control pulses (electrical or optical), can only be applied to the surface of the heart.…”

Section: Discussionmentioning

confidence: 99%

In silico optical control of pinned electrical vortices in an excitable biological medium

2020

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Vortices of excitation are generic to any complex excitable system. In the heart, they occur as rotors, spirals (2D) and scroll waves (3D) of electrical activity that are associated with rhythm disorders, known as arrhythmias. Lethal cardiac arrhythmias often result in sudden death, which is one of the leading causes of mortality in the industrialized world. Irrespective of the nature of the excitable medium, the rotation of a rotor is driven by its dynamics at the (vortex) core. In a recent study, Majumder et al (2018 eLife 7 e41076) demonstrated, using in silico and in vitro cardiac optogenetics, that light-guided manipulation of the core of free rotors can be used to establish real-time spatiotemporal control over the position, number and rotation of these rotors in cardiac tissue. Strategic application of this method, called 'Attract-Anchor-Drag' (AAD) can also be used to eliminate free rotors from the heart and stop cardiac arrhythmias. However, rotors in excitable systems, can pin (anchor) around local heterogeneities as well, thereby limiting their dynamics and possibility for spatial control. Here, we expand our results and numerically demonstrate, that AAD method can also detach anchored vortices from inhomogeneities and subsequently control their dynamics in excitable systems. Thus, overall we demonstrate that AAD control is one of the first universal methods that can be applied to both free and pinned vortices, to ensure their spatial control and removal from the heart and, possibly, other excitable systems.

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“…Several studies have been also carried out on the hearts of mice, especially in the field of atrial fibrillation (AF). The idea was to modulate the heart rhythm, using light radiation on genetically modified ChR2 proteins [37]. These proteins can activate or inhibit the potassium (K) channel, thus shortening the atrial refractoriness and improving the atrial conduction.…”

Section: Applications In Heart Failurementioning

confidence: 99%

The Impact of Optogenetics on Regenerative Medicine

Spagnuolo

Genovese²,

Lombardo

et al. 2019

Applied Sciences

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Optogenetics is a novel strategic field that combines light (opto-) and genetics (genetic) into applications able to control the activity of excitable cells and neuronal circuits. Using genetic manipulation, optogenetics may induce the coding of photosensitive ion channels on specific neurons: this non-invasive technology combines several approaches that allow users to achieve improved optical control and higher resolution. This technology can be applied to optical systems already present in the clinical-diagnostic field, and it has also excellent effects on biological investigations and on therapeutic strategies. Recently, several biomedical applications of optogenetics have been investigated, such as applications in ophthalmology, in bone repairing, in heart failure recovery, in post-stroke recovery, in tissue engineering, and regenerative medicine (TERM). Nevertheless, the most promising and developed applications of optogenetics are related to dynamic signal coding in cell physiology and neurological diseases. In this review, we will describe the state of the art and future insights on the impact of optogenetics on regenerative medicine.

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Optogenetic termination of atrial fibrillation in mice

Abstract: We provide the first evidence for optogenetic termination of atrial tachyarrhythmia in intact hearts from transgenic as well as wild type mice ex and in vivo. Thus, this report could lay the foundation for the development of implantable devices for pain-free termination of AF.

Cited by 64 publications

References 46 publications

Multifunctional Flexible Biointerfaces for Simultaneous Colocalized Optophysiology and Electrophysiology

Multifunctional Flexible Biointerfaces for Simultaneous Colocalized Optophysiology and Electrophysiology

In silico optical control of pinned electrical vortices in an excitable biological medium

The Impact of Optogenetics on Regenerative Medicine

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