title: 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.
authors.affiliation: Center for Bionics, Korea Institute of Science and Technology (KIST), Seoul, 02792, Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Center for Bionics, Korea Institute of Science and Technology (KIST), Seoul, 02792, Korea.|Korea University of Science and Technology, Daejeon, 34113, Korea.
authors.forename: Jin Ki
authors.initials: JK
authors.lastname: Hong
authors.affiliation: Center for Bionics, Korea Institute of Science and Technology (KIST), Seoul, 02792, Korea.|Department of Electronics Engineering, Ewha Womans University, Seoul, 03760, Korea.
authors.forename: Ja Yun
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Physiology, SBRI, Sungkyunkwan University School of Medicine, Suwon, 16419, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
authors.forename: Kyu-Sung
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Physiology, SBRI, Sungkyunkwan University School of Medicine, Suwon, 16419, Korea.
authors.forename: Tong Mook
authors.initials: TM
authors.lastname: Kang
authors.affiliation: Center for Bionics, Korea Institute of Science and Technology (KIST), Seoul, 02792, Korea.|Korea University of Science and Technology, Daejeon, 34113, Korea.
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Center for Bionics, Korea Institute of Science and Technology (KIST), Seoul, 02792, Korea.
authors.forename: Jun-Kyo Francis
authors.initials: JF
authors.lastname: Suh
mesh_terms: D000818:Animals; D000075402:Channelrhodopsins / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000528:radiation effects; D025602:Halorhodopsins / Q000235:genetics; D066298:In Vitro Techniques; D008027:Light; D059411:Lower Urinary Tract Symptoms / Q000473:pathology* / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects / Q000528:radiation effects; D016297:Mutagenesis, Site-Directed; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D001743:Urinary Bladder / Q000166:cytology / Q000502:physiology*; D014554:Urination
chemical_list: D000075402:Channelrhodopsins; D025602:Halorhodopsins; D015232:Dinoprostone