Year: 2019
Type: article
Abstract: You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (MP62)1 Apr 2019MP62-04 CLOSED LOOP OPTOGENETIC NEUROMODULATION OF BLADDER FUNCTION Aaron Mickle*, Sang Min Won, Kyung Nim Noh, Jangyeol Yoon, Kate Meacham, Lisa McIlvried, Bryan Copits, Vijay Samineni, Henry Lai, John Rogers, and Robert Gereau Aaron Mickle*Aaron Mickle* More articles by this author , Sang Min WonSang Min Won More articles by this author , Kyung Nim NohKyung Nim Noh More articles by this author , Jangyeol YoonJangyeol Yoon More articles by this author , Kate MeachamKate Meacham More articles by this author , Lisa McIlvriedLisa McIlvried More articles by this author , Bryan CopitsBryan Copits More articles by this author , Vijay SamineniVijay Samineni More articles by this author , Henry LaiHenry Lai More articles by this author , John RogersJohn Rogers More articles by this author , and Robert GereauRobert Gereau More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556827.86596.70AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Bioelectronic technologies that are capable of modulating activity of the peripheral nervous system offer powerful options in targeted treatment of organ dysfunction and pain, with features that have the potential to bypass limitations of traditional pharmacological approaches. Here we introduce a miniaturized, fully implantable wireless bio-optoelectronic system that circumvents these challenges by monitoring and modulating bladder function in an active, closed-loop fashion through optogenetic, as opposed to electrical, modulation of bladder-projecting sensory afferents. METHODS: The resulting technology includes a wireless strain gauge that wraps around the bladder, enabling measurement of changes bladder size, and includes integrated microscale light emitting diodes (µLEDs) to allow optogenetic modulation. This approach avoids the use of potentially damaging nerve-interfacing electrodes or implantation of invasive bladder catheters, which can disrupt normal bladder function. The strain gauge and μLEDs operate via an implanted Bluetooth base station that allows for wireless monitoring of bladder activity and enables closed-loop control via optogenetics. Utilizing herpes simplex viral (HSV) vectors to deliver the light-activated proton pump, archaerhodopsin (Arch, which can inhibit neuronal firing) to bladder afferents. RESULTS: We can chronically measure bladder activity using the implanted strain gauge and these measurements correlate with traditional bladder pressure cystometry, void volumes and overall bladder size. Using the wireless optoelectronic strain gauge, we can clearly identify the onset of altered voiding behaviors associated with bladder inflammation, and activation of Arch in bladder afferents can reduce the number of void associated with inflammation. We programed our software to recognize these changes in bladder frequency associated with bladder inflammation and to activate the µLEDs. Closed loop activation of µLEDs reduced voiding frequency in the Arch-injected animal compared to eYFP. CONCLUSIONS: These advances will enable novel insight into the mechanisms of bladder control and pain as well as lay the groundwork for potential optogenetic and closed loop interventions to treat other visceral diseases. Source of Funding: This work was funded by an NIH Directors Transformative Research Award TR01 NS081707 (RWG and JAR), NIH SPARC Award via the NIBIB of the NIH award U18 EB021793 (RWG and JAR), R01 NS42595 (RWG), NRSA F32 DK115122 (ADM), the McDonnell Center for Cellular and Molecular Neurobiology Postdoctoral Fellowship (ADM), K01 DK115634 and the Urology Care Foundation Research Scholars Program and Kailash Kedia Research Scholar Fellowship (VKS). Saint Louis, MO; Evanston, IL; Saint Louis, MO; Evanston, IL; Saint Louis, MO© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e888-e888 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aaron Mickle* More articles by this author Sang Min Won More articles by this author Kyung Nim Noh More articles by this author Jangyeol Yoon More articles by this author Kate Meacham More articles by this author Lisa McIlvried More articles by this author Bryan Copits More articles by this author Vijay Samineni More articles by this author Henry Lai More articles by this author John Rogers More articles by this author Robert Gereau More articles by this author Expand All Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2940758641