Abstract: TH-PO0251
Daily Repeated Optogenetic Vagus Nerve Stimulation Attenuates Renal Fibrosis in Unilateral Ureteral Obstruction
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Shimoyama, Kotaro, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Umene, Ryusuke, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Wu, Chia-Hsien, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Nakamura, Yasuna, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Inoue, Tsuyoshi, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
Background
Vagus nerve stimulation (VNS) modulates immune responses through neuroimmune pathways, including the cholinergic anti-inflammatory pathway, and has been shown to protect against acute kidney injury. However, its impact on chronic kidney disease and renal fibrosis remains poorly understood. A major technical limitation is that conventional VNS requires repeated anesthesia, surgical exposure of the nerve, and electrode placement, making chronic and reproducible stimulation difficult. To overcome this limitation, we developed a remote-controlled optogenetic VNS system that enables repeated stimulation in awake mice.
Methods
To overcome these limitations, we developed a minimally invasive system that enables repeated VNS in awake mice. This system applies optogenetics, a technique that allows neural activity to be controlled by light. We used ChAT-Cre:ChR2 mice, in which blue light-sensitive channelrhodopsin-2 (ChR2) is selectively expressed in cholinergic vagal efferent fibers. A miniature blue LED was implanted near the cervical vagus nerve, and the LED wire was passed subcutaneously and connected to an infrared receiver mounted on the skull. By transmitting infrared signals from outside the body, we established a remote-controlled optogenetic VNS system that enables repeated stimulation in awake mice.
Results
The functionality of this system was confirmed by recording vagal nerve activity during optical stimulation. We next applied this technique to a mouse model of renal fibrosis induced by unilateral ureteral obstruction (UUO). Optogenetic VNS was delivered once daily for 7 days at 5 Hz for 10 minutes. Daily VNS significantly reduced the expression of fibrosis-related genes, including Acta2, Tgfb1, Col1a1, Col3a1, and Fn1, as assessed by renal qPCR. Histological analysis using Picrosirius Red staining also demonstrated a reduction in fibrotic area, indicating marked attenuation of renal fibrosis. Single-cell RNA sequencing of the kidney further revealed that VNS altered macrophage subpopulations and increased Trem2-positive macrophages, which are associated with tissue repair programs.
Conclusion
We established a remote-controlled optogenetic VNS system that enables repeated stimulation in awake mice. Daily VNS attenuated renal fibrosis in the UUO model and was associated with remodeling of renal macrophage subpopulations.