Optogenetics in understanding mechanisms of acute kidney injury

Abstract

Background: No approved pharmacological agents are available for the treatment and prevention of acute kidney injury (AKI). The nervous system has been reported to play an important role, directly or indirectly via the immune system, in the pathophysiology of AKI. Neuromodulation, such as vagus nerve stimulation and pulsed ultrasound, is emerging as an innovative therapeutic treatment for various diseases including AKI. However, lack of effective methods to selectively stimulate or inhibit neurons has hampered the complete understanding of the roles of the nervous system in AKI because electrical stimulation is nonspecific for cell types. Summary: A novel technique called optogenetics optically controls cells in living tissues, typically neurons, which have been genetically modified to express light-sensitive opsins. For example, channelrhodopsin-2 (ChR2), an opsin, is a nonselective cation channel residing in a cell membrane, which rapidly opens its gate after exposing to monochromatic light in the "blue" wavelength. Unlike electrodes, blue light can selectively depolarize ChR2-expressing neurons, mainly via the Na+ entry, evoking an action potential. Optogenetics that use ChR2 and several variants to modulate kinetic properties and inhibitory opsins help in understanding the roles of the nervous system in AKI, thus leading to a clinical application of neuromodulation to AKI treatment.