Optogenetics: Background, Methodological Advances and Potential Applications for Cardiovascular Research and Medicine

Abstract

Optogenetics is an elegant approach of precisely controlling and monitoring the biological functions of a cell, group of cells, tissues, or organs with high temporal and spatial resolution by using optical system and genetic engineering technologies. The field evolved with the need to precisely control neurons and decipher neural circuity and has made great accomplishments in neuroscience. It also evolved in cardiovascular research almost a decade ago and has made considerable progress in both in vitro and in vivo animal studies. Thus, this review is written with an objective to provide information on the evolution, background, methodical advances, and potential scope of the field for cardiovascular research and medicine. We begin with a review of literatures on optogenetic proteins related to their origin, structure, types, mechanism of action, methods to improve their performance, and the delivery vehicles and methods to express such proteins on target cells and tissues for cardiovascular research. Next, we reviewed historical and recent literatures to demonstrate the scope of optogenetics for cardiovascular research and regenerative medicine and examined that cardiac optogenetics is vital in mimicking heart diseases, understanding the mechanisms of disease progression and also in introducing novel therapies to treat cardiac abnormalities, such as arrhythmias. We also reviewed optogenetics as promising tools in providing high-throughput data for cardiotoxicity screening in drug development and also in deciphering dynamic roles of signaling moieties in cell signaling. Finally, we put forth considerations on the need of scaling up of the optogenetic system, clinically relevant in vivo and in silico models, light attenuation issues, and concerns over the level, immune reactions, toxicity, and ectopic expression with opsin expression. Detailed investigations on such considerations would accelerate the translation of cardiac optogenetics from present in vitro and in vivo animal studies to clinical therapies.

Optogenetic Cardiac Pacing and Its Applications

“…The clinical translation of cardiac optogenetics for human application is moving towards use as a tool in larger mammalian animal models [58]. Optogenetics may restore normal heart rhythm to increase the overall quality of life and action potential duration of ChR2-or NpHR can be modulated in opsin-expressing rat cardiomyocytes [34,[59][60][61]. Optogenetics may potentially have a therapeutic role in treating heart diseases.…”

Drug Screening with Genetically Encoded Fluorescent Sensors: Today and Tomorrow

“…The development of voltage sensitive dyes and, later, genetically encoded voltage indicators (GEVIs) and optogenetic actuators (reviewed in [ 69 , 70 , 71 , 72 , 73 ]) opened opportunities for all-optical electrophysiology. An important step towards this goal was made by Hochbaum et al when they developed the improved voltage indicators QuasAr1 and QuasAr2 on the basis of Archaerhodopsin 3 (Arch) from Halorubrum sodomense [ 74 ].…”

Future Perspectives and New “Frontiers” in Cardiac Rhythmology

“…Other innovative approaches, however, appear ready for a formidable expansion. Optogenetics is an attempt to control and monitor the biological functions of a cell, group of cells, tissue, by using optical systems and genetic engineering technologies (39). Stem cell-based therapies aim to regenerate damaged cardiac muscle by replacing dead tissue with new contracting myocytes or replace misfunctioning ion channels (40) and virtual electrophysiology to model bioelectronic heart-on-a-chip models for studying the effects of different noxa on cardiac function (41).…”