Abstract: FR-PO149
Optogenetic Stimulation of Kidney Sympathetic Nerves as a New Protective Approach to AKI
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Umene, Ryusuke, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
- Wu, Chia-Hsien, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
- Washimine, Norito, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
- Matsuo, Sayumi, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
- Nishino, Tomoya, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
- Inoue, Tsuyoshi, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
Background
Acute kidney injury (AKI) is a life-threatening condition with a poor prognosis. Once AKI develops, there is a high risk of developing chronic kidney disease (CKD), a condition that carries a high risk of cardiovascular disease and death. Even though the number of patients with AKI is increasing every year, there is currently no curative treatment for kidney disease, highlighting the need for innovative therapies. Recent research suggests that renal sympathetic nerve modulation may offer protective effects. Traditional methods lack specificity, so this study employs optogenetics, a minimally invasive technique for precise neural activation, to investigate the renal protective mechanisms of sympathetic nerve stimulation.
Methods
Using optogenetics, we specifically stimulated renal sympathetic nerves in transgenic mice expressing channelrhodopsin-2 in sympathetic neurons (DbHCre-ChR2). Blue light was directed at the kidneys to stimulate these nerves. We optimized stimulation parameters (duration, frequency, intensity) by monitoring blood pressure, heart rate, and renal norepinephrine levels. To assess protective effects, we induced AKI with bilateral renal ischemia-reperfusion injury (IRI) and LPS-induced sepsis models. Single-cell RNA sequencing (scRNA-seq) on renal tissues identified cells receiving sympathetic signals and their interactions.
Results
Optogenetic stimulation of renal sympathetic nerves significantly reduced renal injury in acute kidney injury models. Protection was observed against bilateral renal IRI following nerve stimulation. scRNA-seq revealed that tubular epithelial cells responded to sympathetic stimulation, with upregulated expression of protective factors, indicating direct renal protection via the sympathetic nervous system, independent of systemic immune modulation.
Conclusion
This study introduces a novel optogenetics-based method for specific stimulation of renal sympathetic nerves, demonstrating its potential to reduce renal injury. The identification of specific cellular responses and protective mechanisms advances our understanding of the renal protective role of sympathetic nerves. These findings pave the way for developing new therapeutic devices and drugs targeting renal sympathetic modulation, offering promising prospects for kidney disease treatment.
Funding
- Private Foundation Support