Non-invasive red-light optogenetic control of Drosophila cardiac function

Men, Jing; Li, Airong; Jerwick, Jason; Li, Zilong; Tanzi, Rudolph E.; Zhou, Chao

doi:10.1038/s42003-020-1065-3

Cited by 14 publications

(11 citation statements)

References 60 publications

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“…Figure 3h and Figure S10, Supporting Information, summarize the temperature increases on the surface of the blue m‐LEDs in air at different frequencies and irradiances relevant to the optogenetics illumination parameters for excitatory and inhibitory opsins. [ 41–44 ] For example, the maximum temperature increase is within 0.6 °C for duty cycles ≤5% when the blue m‐LEDs operate at 1 or 7 Hz with an output irradiance of 25.3 mW mm −2 , which falls well below the thermal thresholds (<2 °C) for cardiac tissue damage. [ 45 ]…”

Section: Resultsmentioning

confidence: 99%

Flexible Electro‐Optical Arrays for Simultaneous Multi‐Site Colocalized Spatiotemporal Cardiac Mapping and Modulation

Obaid

Chen

Madrid

et al. 2022

Advanced Optical Materials

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disease arises from asynchrony and abnormalities in the complex and coordinated electro-mechanical properties over time and space. Therefore, devices that allow monitoring and controlling of the spatiotemporal dynamics of cardiac activity are crucial for unraveling the pathophysiology of heart disease and developing effective treatment therapies in clinical cardiology practice. Implantable electronic pacemakers play an essential role in treating various types of arrhythmias and heart failure and studying cardiac physiology by changing the membrane potential and triggering an action potential with an electric current. [3,4] However, electrical stimulation can lead to adverse effects on cell health and integrity due to the cell membrane electroporation and redox processes. [5,6] The electrical fields created by the stimulation electrodes will generate electrical crosstalk between stimulation and recording electrodes and result in recording artifacts. [7] Furthermore, electrical stimulation is unable to target specific subtypes of cardiac cells. Optogenetics uses light to modulate the activity of genetically targeted cell types through photosensitive ion channels and pumps. [8] Despite its initial use in neuroscience research to control neural circuits, [8,9] optogenetics has now been applied as a promising tool in cardiology for pain-free, low-energy optical pacing, and defibrillation with cell-type specificity. [10][11][12] In addition, cardiac optogenetics generally interferes less with simultaneous electrical readout of cardiac activity compared to electrical stimulation. Currently, cardiac optogenetics is primarily used in in vitro and ex vivo cardiac studies with cell cultures or explanted perfused hearts. [13][14][15][16][17] More in vivo research is crucially needed to fully exploit the unique opportunities cardiac optogenetics offers for mechanistic investigations of heart function in health and disease.Small animal models such as mice and rats are the main rodent species that could be genetically engineered for in vivo cardiac optogenetics research and their heart electrophysiology is a good approximation of the human electrophysiology. [18] Implantable cardiac devices that combine precise light delivery to targeted heart regions of small animals with electrophysiological readout capabilities remain a major technological Bioelectronic devices that allow simultaneous accurate monitoring and control of the spatiotemporal patterns of cardiac activity provide an effective means to understand the mechanisms and optimize therapeutic strategies for heart disease. Optogenetics is a promising technology for cardiac research due to its advantages such as cell-type selectivity and high space-time resolution, but its efficacy is limited by the insufficient number of modulation channels and lack of simultaneous spatiotemporal mapping capabilities in current implantable cardiac optogenetics tools available for in vivo investigations. Here, soft implantable electro-optical cardiac devices integrating multilayered highly ...

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Section: Resultsmentioning

confidence: 99%

Flexible Electro‐Optical Arrays for Simultaneous Multi‐Site Colocalized Spatiotemporal Cardiac Mapping and Modulation

Obaid

Chen

Madrid

et al. 2022

Advanced Optical Materials

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“…Such approaches can facilitate in-depth experimental studies of valveless pumping which otherwise require numerical simulations and modeling. Recently, optogenetic pacing of the embryonic heart has been achieved, enabling both increases and decreases in the heartbeat rate as well as cardiac arrest [ 71 , 72 , 73 ]. Particularly for the mouse model, optogenetic pacing was shown to induce hemodynamic changes in the heart [ 74 ], which, together with the possibility of highly-localized pacing or disruption, suggests a potentially useful integration with pumping analysis to further assess the pumping dynamics during mammalian cardiogenesis.…”

Section: Emerging Concepts and Analysesmentioning

confidence: 99%

Following the Beat: Imaging the Valveless Pumping Function in the Early Embryonic Heart

Wang

Larina

2022

JCDD

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In vertebrates, the coordinated beat of the early heart tube drives cardiogenesis and supports embryonic growth. How the heart pumps at this valveless stage marks a fascinating problem that is of vital significance for understanding cardiac development and defects. The developing heart achieves its function at the same time as continuous and dramatic morphological changes, which in turn modify its pumping dynamics. The beauty of this muti-time-scale process also highlights its complexity that requires interdisciplinary approaches to study. High-resolution optical imaging, particularly fast, four-dimensional (4D) imaging, plays a critical role in revealing the process of pumping, instructing numerical modeling, and enabling biomechanical analyses. In this review, we aim to connect the investigation of valveless pumping mechanisms with the recent advancements in embryonic cardiodynamic imaging, facilitating interactions between these two areas of study, in hopes of encouraging and motivating innovative work to further understand the early heartbeat.

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“…In this study, we used Drosophila melanogaster as the model organism to assess the opsin performance in cardiac tissue. Drosophila has been very efficient for optogenetic pacing using different opsins and has several benefits such as short *chaozhou@wustl.edu; https://zlab.wustl.edu/ light cycle and easy genetic manipulations, etc 7 . The optogenetic pacing was performed using a LED module coupled with optical coherence microscopy (OCM) to monitor the process, which is a non-invasive three-dimension imaging modality.…”

Section: Introductionmentioning

confidence: 99%

Optimization of optogenetic control of Drosophila cardiac function using ChRmine opsin

Wang

Gracheva

Matt

et al. 2023

Optogenetics and Optical Manipulation 2023

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Optogenetics allows non-invasive control of cardiac function by inducing physiological heart distress. The main challenge for optogenetic pacing is relatively shallow light penetration into biological tissue. Recently, ChRmine was reported as an excitatory opsin that can respond to much lower light power which induces a larger cellular membrane electrical current than the previously characterized opsins. It has been shown that ChRmine expressed deep inside the mouse brain (~7 mm) sensed the external illumination leading to mouse behavior change. However, the ChRmine application for optogenetic cardiac function control has not been optimized yet. This study demonstrates the feasibility of ChRmine-mediated restorable tachycardiac pacing in Drosophila (fruit fly) hearts non-invasively and discusses the influence of different parameters of both optical settings and gene expression levels to achieve its optimal performance. custom optical coherence microscopy (OCM) was synchronized with the illumination module to monitor the dynamics of the fly heart while light pulses were applied. The quantification of cardiac function was performed by lab-developed software FlyNet 2.0+. The results demonstrate successful pacing at designed frequencies higher than the resting heart rate in ChRmine flies. Irradiance power density and pulse width were tested for minimal light power input. Illumination protocols were set up to provide pacing control. Different transcriptional activator strains were crossed in to enhance transgenic ChRmine expression. Opsin ligand concentration in Drosophila media was adjusted for saturating opsin membrane channel opening. Red light wavelengths (617 or 656 nm) were considered to promote penetration depth for optogenetic activation. This study will serve as practical guidance for performing optogenetic pacing using ChRmine opsin.

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Non-invasive red-light optogenetic control of Drosophila cardiac function

Cited by 14 publications

References 60 publications

Flexible Electro‐Optical Arrays for Simultaneous Multi‐Site Colocalized Spatiotemporal Cardiac Mapping and Modulation

Flexible Electro‐Optical Arrays for Simultaneous Multi‐Site Colocalized Spatiotemporal Cardiac Mapping and Modulation

Following the Beat: Imaging the Valveless Pumping Function in the Early Embryonic Heart

Optimization of optogenetic control of Drosophila cardiac function using ChRmine opsin

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