The pathophysiology of OAB is unknown. While there are proposed etiologies including detrusor smooth muscle and neural mechanisms, the potential contribution of the bladder urothelial cells (BUC) to OAB is a new avenue of inquiry. The University of Maryland Interdisciplinary Research Center (UM-IRC) in benign urology will perform a planning study in which bladder urothelial biopsies will be obtained from subjects with no urinary incontinence and no voiding symptoms (controls) and from subjects with OAB symptoms (urge incontinence). Primary BUC cultures derived from these biopsies will be studied in the laboratories of the Program Director (Chai) and the two co-principal investigators (Birder, Keay). Because these labs already have independent funding, the multiple PI approach for the UM-IRC is utilized. The intent of the laboratory studies Is to obtain preliminary laboratory data which then can help statistically power the next OAB trial using laboratory objective measures as primary outcomes. The three phenotypes of BUC that will be measured are expression of intracellular polyamines, expression of tight junction proteins, and cellular mechanosensitivity measured by adenosine triphosphate (ATP) release in response to hypo-osmotic and chemical stimuli. Early preliminary data suggest alterations in all three of these phenotypes in OAB BUC. During this planning phase, the UM-IRC will firmly establish collaboration among the three laboratories which are already active in basic bladder urothelial biologic studies. An advisory panel will be used to govern the UM-IRC during the planning phase. Because the most important factor during the first two year is recruitment of OAB and control subjects to undergo bladder urothelial biopsies, the advisory panel will maintain constant surveillance of the recruitment numbers in addition to subject safety. The UM-IRC will utilize the Univ of Maryland Continence and Pelvic Center for recruitment. There are several OAB clinical trials currently ongoing which can help with the recruitment for this proposal. Based on the budgetary constraints of the RFA, 10 OAB and 10 control subjects will be enrolled. The UM-IRC will utilize an interdisciplinary approach in performing translational research linking urothelial pathophysiology to OAB.
Overactive bladder (OAB) is a highly prevalent condition affecting over 16 million people in the USA. Diagnosis and treatment for OAB remains rudimentary and rely almost exclusively on patient reported symptoms. By increasing the understanding of this condition with basic science experiments, we hope to understand the causes for OAB. Specifically we will focus on the role of the bladder lining cells (urothelial CRIIS) in the cause of OAB.
| Birder, L A; Wolf-Johnston, A S; Sun, Y et al. (2013) Alteration in TRPV1 and Muscarinic (M3) receptor expression and function in idiopathic overactive bladder urothelial cells. Acta Physiol (Oxf) 207:123-9 |
