Transdermal light neuromodulation: Optogenetics in the murine urinary tract

Wallace, Shannon L.; Kelley, Robert S.; Mehta, Shailja; Descalzi, Giannina; Fantl, J. Andrew; Ascher‐Walsh, Charles

doi:10.1002/nau.23458

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…Researchers have also designed wireless bio-optoelectronic implants to be placed around the bladder for the optogenetic modulation of bladder function. ,, However, these devices are complex and require invasive surgical implantation. Transdermal illumination is a potential choice for noninvasive optogenetic approaches, , while achieving deep-tissue optogenetic stimulation becomes challenging when targeting deeply located organs like the bladder, even with red-shifted variants of channelrhodopsin (ReaChR, responding to 590 to 630 nm) . NIR can more effectively penetrate tissues than visible light due to the low scattering and absorption of photons and has been developed as a powerful tool for minimally invasive assessment and intervention therapy.…”

Section: Discussionmentioning

confidence: 99%

Minimally Invasive Bladder Stimulation via Upconversion Nanoparticle-Mediated Optogenetics

Zhou,

Wang,

Liao

2024

ACS Appl. Nano Mater.

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Currently, there are no clinically proven alternative treatments for inducing or enhancing bladder contractions. In this study, we applied optogenetics to modulate bladder function, successfully inducing contractions with 475 nm blue light after transfecting channelrhodopsin-2 (ChR2) into bladder smooth muscle cells. However, it requires laparotomy and bladder exposure due to restricted tissue penetration of visible light. Hence, we developed a minimally invasive approach utilizing tissue penetrating near-infrared (NIR) light via upconversion nanoparticles (UCNPs) as an intermediary for bladder control. The core−shell UCNPs NaYF 4 :Yb/Tm@PEG were designed. Excited at 980 nm, UCNPs emitted predominantly at 475 nm, matching the excitation wavelength of ChR2. We reasoned the feasibility of the UCNPs-mediated optogenetics system for its efficacy and safety. In our experiment, we confirmed that the blue light emitted by UCNPs under NIR is sufficient to activate ChR2 and induce cation influx in bladder smooth muscle cells. Moreover, we confirmed that NIR has low cell toxicity and acceptable photothermal effects. No significant tissue toxicity of UNCPs was detected. Then, we performed ex vivo bladder pressure recording and in vivo cystometry 4 weeks after UCNPs injection and ChR2 transfection. An 8.0 W 980 nm transdermal illumination was delivered from the optical laser, with no need for invasive procedures to expose the bladder. The result showed that NIR successfully induced bladder contractions in the ChR2-transfected bladder with the intermediation of UCNPs. Compared with spontaneous voiding, NIRinduced voiding exhibited higher maximum detrusor pressure and micturition volume. These findings demonstrated that UCNPsmediated optogenetics can serve as a minimally invasive approach to optical bladder control.

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Section: Discussionmentioning

confidence: 99%

Minimally Invasive Bladder Stimulation via Upconversion Nanoparticle-Mediated Optogenetics

Zhou,

Wang,

Liao

2024

ACS Appl. Nano Mater.

View full text Add to dashboard Cite

show abstract

“…Several investigations using optogenetics have been conducted into modulation of the sensory neurons innervating the bladder. Wallace et al preliminary explored the role of optogenetics in relieving bladder pain by injecting AAV6 with the excitatory opsin ChR2(H134R) into the sciatic nerves (43). Although the study was not powered to show statistical significance, the mice experienced inhibition of bladder pain along with exhibition of foot pain under blue light.…”

Section: Application In Sensory Neurons Innervating the Bladdermentioning

confidence: 99%