Conclusions
We developed a RC model that mimics the human pathology and functional changes. Furthermore, radiation exposure attenuates the urothelial integrity long-term allowing for potential continuous irritability of the bladder wall from exposure to urine. Future studies will focus on the underlying molecular changes associated with this condition and investigate novel treatment strategies.
Purpose
Radiation cystitis (RC), a severe inflammatory bladder condition, develops as a side-effect of pelvic radiation therapy in cancer patients. There are currently no effective therapies to treat RC, in part due to the lack of preclinical model systems. In this study, we developed a mouse model for RC and used a small animal radiation research platform (SARRP) to simulate the targeted delivery of radiation as used with human patients.
Results
Radiation was well tolerated as no change in weight was observed in the weeks post treatment, and there was no hair loss at the irradiation sites. Starting at 17 weeks post treatment, micturition frequency was significantly higher in irradiated mice versus control animals. Pathological changes include fibrosis, inflammation, urothelial thinning and necrosis. At a site of severe insult, we observed telangiectasia, absence of Uroplakin-3 and E-cadherin relocalization. Conclusions: We developed a RC model that mimics the human pathology and functional changes. Furthermore, radiation exposure attenuates the urothelial integrity long-term allowing for potential continuous irritability of the bladder wall from exposure to urine. Future studies will focus on the underlying molecular changes associated with this condition and investigate novel treatment strategies.