Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation

Nyns, Emile C.A.; Portero, Vincent; Deng, Shanliang; Jin, Tianyi; Harlaar, Niels J.; Bart, Cindy I.; Brakel, Thomas J. van; Palmen, Meindert; Hjortnaes, Jesper; Ramkisoensing, Arti A.; Zhang, Guo Qi; Poelma, R. H.; Ördög, Balázs; Vries, Antoine A.F. de; Pijnappels, Daniël A.

doi:10.1111/joim.13654

Cited by 7 publications

(2 citation statements)

References 23 publications

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“… 90 Implantable multi-LED devices delivering apical or transthoracic illumination with a closed chest have enabled in vivo arrhythmia termination in pathologically remodelled rat hearts, expressing ReaChR. 122 , 123 …”

Section: Applications Of Optogenetics In Cardiac Electrophysiologymentioning

confidence: 99%

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review

Baines,

Sha,

Kalla

et al. 2024

Europace

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State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilises light-sensitive ion channels and pumps to realise contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell-cell interactions. The merging of optogenetics and optical mapping techniques for ‘all-optical’ electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial-temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturised, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimising therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies.

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Section: Applications Of Optogenetics In Cardiac Electrophysiologymentioning

confidence: 99%

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review

Baines,

Sha,

Kalla

et al. 2024

Europace

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“…However, various red-shifted ChR variants have presented significant deficiencies hampering optimal implementation in the heart. Red-shifted ChR variants currently used in cardiac pacing and defibrillation approaches include red activatable channelrhodopsin (ReaChR) and ChRmine [ 20 , 39 – 42 ], which exhibit a peak activation wavelength of ± 610 nm and ± 540 nm, respectively [ 33 , 52 ]. Despite their red-shifted peak activation wavelength, both ReaChR and ChRmine exhibit a wide activation spectrum [ 33 , 52 ], indicating that these channels would also be activated by blue light.…”

Section: Optogenetic Actuatorsmentioning

confidence: 99%

Recent advances and current limitations of available technology to optically manipulate and observe cardiac electrophysiology

Marchal,

Biasci,

Yan

et al. 2023

Pflugers Arch - Eur J Physiol

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Optogenetics, utilising light-reactive proteins to manipulate tissue activity, are a relatively novel approach in the field of cardiac electrophysiology. We here provide an overview of light-activated transmembrane channels (optogenetic actuators) currently applied in strategies to modulate cardiac activity, as well as newly developed variants yet to be implemented in the heart. In addition, we touch upon genetically encoded indicators (optogenetic sensors) and fluorescent dyes to monitor tissue activity, including cardiac transmembrane potential and ion homeostasis. The combination of the two allows for all-optical approaches to monitor and manipulate the heart without any physical contact. However, spectral congestion poses a major obstacle, arising due to the overlap of excitation/activation and emission spectra of various optogenetic proteins and/or fluorescent dyes, resulting in optical crosstalk. Therefore, optogenetic proteins and fluorescent dyes should be carefully selected to avoid optical crosstalk and consequent disruptions in readouts and/or cellular activity. We here present a novel approach to simultaneously monitor transmembrane potential and cytosolic calcium, while also performing optogenetic manipulation. For this, we used the novel voltage-sensitive dye ElectroFluor 730p and the cytosolic calcium indicator X-Rhod-1 in mouse hearts expressing channelrhodopsin-2 (ChR2). By exploiting the isosbestic point of ElectroFluor 730p and avoiding the ChR2 activation spectrum, we here introduce a novel optical imaging and manipulation approach with minimal crosstalk. Future developments in both optogenetic proteins and fluorescent dyes will allow for additional and more optimised strategies, promising a bright future for all-optical approaches in the field of cardiac electrophysiology.

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Nongenetic Optical Modulation of Pluripotent Stem Cells Derived Cardiomyocytes Function in the Red Spectral Range

Ronchi,

Galli,

Tullii

et al. 2023

Advanced Science

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Optical stimulation in the red/near infrared range recently gained increasing interest, as a not‐invasive tool to control cardiac cell activity and repair in disease conditions. Translation of this approach to therapy is hampered by scarce efficacy and selectivity. The use of smart biocompatible materials, capable to act as local, NIR‐sensitive interfaces with cardiac cells, may represent a valuable solution, capable to overcome these limitations. In this work, a far red‐responsive conjugated polymer, namely poly[2,1,3‐benzothiadiazole‐4,7‐diyl[4,4‐bis(2‐ethylhexyl)−4H‐cyclopenta[2,1‐b:3,4‐b’]dithiophene‐2,6‐diyl]] (PCPDTBT) is proposed for the realization of photoactive interfaces with cardiomyocytes derived from pluripotent stem cells (hPSC‐CMs). Optical excitation of the polymer turns into effective ionic and electrical modulation of hPSC‐CMs, in particular by fastening Ca2+ dynamics, inducing action potential shortening, accelerating the spontaneous beating frequency. The involvement in the phototransduction pathway of Sarco‐Endoplasmic Reticulum Calcium ATPase (SERCA) and Na+/Ca2+ exchanger (NCX) is proven by pharmacological assays and is correlated with physical/chemical processes occurring at the polymer surface upon photoexcitation. Very interestingly, an antiarrhythmogenic effect, unequivocally triggered by polymer photoexcitation, is also observed. Overall, red‐light excitation of conjugated polymers may represent an unprecedented opportunity for fine control of hPSC‐CMs functionality and can be considered as a perspective, noninvasive approach to treat arrhythmias.

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Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation

Cited by 7 publications

References 23 publications

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review

Recent advances and current limitations of available technology to optically manipulate and observe cardiac electrophysiology

Nongenetic Optical Modulation of Pluripotent Stem Cells Derived Cardiomyocytes Function in the Red Spectral Range

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