Millions of people in the United States suffer from bladder dysfunction and pain caused by interstitial cystitis/bladder pain syndrome and overactive bladder. The underling pathologies for many of these diseases are poorly understood and this is the primary reason why most current treatments are ineffective. To address this issue, our group has designed and tested an implantable wireless optoelectronic system to monitor and modulate bladder function. Our hyper-conformal strain gauge wraps around the bladder and as the bladder expands, changes in geometry of the device linearly increases resistance which can then be directly correlated with bladder size or fullness. We have attached microscale light emitting diodes (?LED) to the strain gauge that can be used to activate light-sensitive opsins for optogenetic regulation of neuronal activity. The strain gauge and ?LEDs connect to an implantable base station that allows for wireless control and monitoring of bladder activity. This new technology eliminates the need for implantation of potentially-damaging bladder catheters or electrodes, and provides unique access to bladder functionality in the awake, freely-moving rat. I plan to utilize viral delivery of opsins and a novel strain gauge that measures dynamic changes in bladder circumference, to modulate and monitor bladder function, respectively. My preliminary data show that changes in strain gauge resistance correlates to traditional bladder activity measurements like intravesicular pressure, and that virally delivered inhibitory opsin, Archaerhodopsin (Arch), can delay bladder contractions in anesthetized rats. I plan to test the ability of virally transduced Arch expressed in bladder afferents to reduce frequency and increase voiding volume after cyclophosphamide (CYP) -induced cystitis in awake animals (Aim 1a and b). I also plan to use our newly developed wireless technology to implement a closed-loop system that can recognize increased frequency of bladder contractions and initiate optogenetic inhibition to normalize voiding (Aim 1c). Bladder pain is the most common complaint of patients suffering from IC/BPS. Using our wireless ?LED strain gauge, I plan to determine whether activation of activation of virally transduced Arch, in bladder afferents, is sufficient to attenuate bladder hypersensitivity in rats with CYP-induced cystitis. This sensitivity will be assayed by visceromotor response, abdominal sensitivity and real time place preference assays (Aim 2). Implementation of this new technology will provide unique access to understanding bladder functionality without the need for implantation of potentially damaging bladder catheters or electrodes. This technology could thus lead to novel insights into the mechanisms of bladder control and pain. Additionally, the refinement of this novel technology and viral delivery methods for optogenetic channels, could lead to development of future therapies for patients with bladder pain and dysfunction.
Millions of people in the United States suffer from bladder dysfunction/pain caused by interstitial cystitis/bladder pain syndrome and underlying pathologies for many of these diseases are poorly understood. The goal of this project will be to gain a better understanding of the role of bladder afferents in interstitial cystitis and further develop technology that can be used to study and treat the disease. The long term goal of the project is to develop targeted closed loop therapies for the treatment of patients with interstitial cystitis/bladder pain syndrome.
| Mickle, Aaron D; Gereau 4th, Robert W (2018) A bright future? Optogenetics in the periphery for pain research and therapy. Pain 159 Suppl 1:S65-S73 |
| Noh, Kyung Nim; Park, Sung Il; Qazi, Raza et al. (2018) Miniaturized, Battery-Free Optofluidic Systems with Potential for Wireless Pharmacology and Optogenetics. Small 14: |
