Optogenetic control of peripheral nerves: A novel approach to modulation of detrusor contractility in vivo

The increasing prevalence of lower urinary tract symptoms (LUTS), particularly voiding dysfunction, has become a significant concern in aging societies. Conventional treatments, including pharmacotherapy and sacral neuromodulation, offer limited efficacy or involve invasive procedures. There is a pressing need for novel, precise, and minimally invasive neuromodulation techniques to restore bladder contractility without compromising continence.

We developed an in vivo optogenetic approach to modulate bladder detrusor activity by delivering an adeno-associated virus (AAV9-hSyn-SOUL) encoding a light-sensitive ion channel directly into the bladder wall of Sprague-Dawley rats. Four weeks post-injection, cystometry was conducted to evaluate bladder responses to blue light (473 nm) stimulation. Histological analysis confirmed transgene expression in peripheral nerves.

Optical stimulation significantly increased intravesical pressure in all vector-injected rats, as confirmed by cystometric analysis. Urinary interval and voided volume showed no significant change following stimulation. Immunofluorescence staining revealed co-localization of SOUL expression with the peripheral nerve marker peripherin in the bladder wall.

Compared to electrical stimulation and pharmacologic agents, this optogenetic approach provided targeted and reversible control of bladder contractions without requiring transgenic animal models or systemic exposure. It offers a less invasive alternative to sacral neuromodulation with improved specificity.

This study demonstrates that optogenetic stimulation of the peripheral bladder nerves using AAV-mediated SOUL expression effectively enhances detrusor contractility while preserving voiding function. These findings support the feasibility of a light-controlled, minimally invasive neuromodulation strategy for the treatment of voiding dysfunction.