Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

Abstract

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

Characterization of mouse neuro‐urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation

“…By way of compensation, the DAPM offers the potential to visualize bladder and urethra movements, which can be video captured allowing relation of electrophysiology to the bladder movement . The potential to combine with bladder sheet and Ca 2+ imaging experiments or optogenetic approaches might bring new insights to the relationship of urothelial transmitters and central nervous system activity.…”

Fiber bundle-based integrated platform for wide-field fluorescence imaging and patterned optical stimulation for modulation of vasoconstriction in the deep brain of a living animal

“…Depolarization of smooth muscle cells expressing ChR2 by blue light induces vasoconstriction in brain of SM22-ChR2 mice. Recently, it has been reported that contraction of bladder smooth muscles and cardiovascular smooth muscles can be regulated by ChR2 [29,30]. So, we used ChR2 mice to control cerebral vasoconstriction in vivo through optical light stimulation.…”

Differential Regulation of Bladder Pain and Voiding Function by Sensory Afferent Populations Revealed by Selective Optogenetic Activation

“…Expression of ChR2 in the CNS has been used to study a number of behaviors, including those related to anxiety, learning, and depression (Huber et al, 2008 ; Covington et al, 2010 ; Tye et al, 2011 ). Recently, optogenetic modulation of bladder smooth muscle was shown to elicit voiding in vivo (Park et al, 2017 ), and our group demonstrated that inhibition of sensory afferent activity via archaerhodopsin, a light-activated proton pump, attenuates pain-related behavior in the context of bladder inflammation (Samineni et al, 2017a ). The present study is an important addition that demonstrates for the first time the effects of direct, selective neuronal activation of distinct bladder afferents on behavioral correlates of bladder sensation and function.…”