In situ observation of water transport through the urothelium with optical coherence tomography

SignificanceThis study provides the first direct evidence of water transport through the urothelium, traditionally considered impermeable. Using Optical Coherence Tomography (OCT), we observe that the urothelium absorbs and expels water under varing concentrations of NaCl, challenging long-held views about its impermeability. The discovery that osmotic stress can induce urothelial damage has significant implications for bladder disorders like interstitial cystitis and overactive bladder, where urothelial integrity is compromised. These findings open new avenues for understanding the mechanisms behind these conditions. AimTraditionally considered impermeable, the urothelium has recently been implicated in water transport due to the presence of aquaporins (AQPs). Despite this, direct evidence of water movement through the urothelium remains elusive. This study aims to provide such evidence by examining urothelial responses to NaCl solutions using Optical Coherence Tomography (OCT). ApproachFresh porcine bladder samples were subjected to OCT imaging to observe urothelial responses under varying osmolarity conditions, using NaCl solutions ranging from 0.31 Osm/L to 2.07 Osm/L. Urothelial thickness was measured pre- and post-NaCl application. Additionally, histological and scanning electron microscopy (SEM) analyses were conducted to assess cellular integrity and damage. ResultsOCT imaging revealed a significant increase in urothelial thickness following deionized water application, indicative of water absorption. Conversely, exposure to higher osmolarity NaCl solutions resulted in urothelial shrinkage, suggesting water efflux. Histological analysis demonstrated intact cellular structures at lower osmolarities (0.31 Osm/L) but significant cellular disruption at higher concentrations ([≥]1.03 Osm/L). SEM analysis corroborated these findings, showing progressive damage to umbrella cells with increasing osmolarity. ConclusionsThis study provides direct evidence that the urothelium is a dynamic barrier capable of water transport, modulated by osmotic gradients. The observed osmotic-induced urothelial damage may have significant implications for the pathophysiology of conditions such as interstitial cystitis and overactive bladder, offering new insights into potential diagnostic and therapeutic strategies.