Related Experiment Video
Updated: Oct 30, 2025
Author Spotlight: Development of a Laser-Induced Shock Wave Animal Model Without Tympanic Membrane Perforation
Published on: March 1, 2024
Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice
Yutaka Koizumi1, Kunio Mizutari2, Satoko Kawauchi3
1Department of Otolaryngology-Head and Neck Surgery, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
Abstract:
Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.
Insights
Cochlear synaptopathy, a cause of hearing loss, may be treatable. Inhibiting rho-associated coiled-coil containing protein kinase (ROCK) with Y-27632 regenerated auditory nerve synapses in mice.
Area of Science:
- Oto-neuroscience
- Regenerative Medicine
Background:
- Cochlear synaptopathy, a disorder of auditory nerve synapses preceding hair cell loss, is a primary cause of sensorineural hearing loss.
- Currently, cochlear synaptopathy lacks effective treatments.
- Rho-associated coiled-coil containing protein kinase (ROCK) inhibition shows neuroprotective and regenerative potential in neural pathways, including the inner ear.
Purpose of the Study:
- To investigate the therapeutic effect of ROCK inhibition on cochlear synaptopathy in a mouse model.
- To validate previous in vitro findings regarding the regenerative capacity of ROCK inhibitors on cochlear nerve damage.
Main Methods:
- Cochlear synaptopathy was induced in mice using laser-induced shock waves (LISW).
- ROCK1/2 expression levels were confirmed to be elevated in the damaged cochlea.
- The ROCK inhibitor Y-27632 was administered locally via the middle ear.
Main Results:
- ROCK inhibition significantly increased the amplitude of wave I in auditory brainstem response.
- A significant increase in the number of synapses was observed in the Y-27632-treated cochlea.
- ROCK inhibition demonstrated a regenerative effect on damaged auditory nerve synapses.
Conclusions:
- ROCK inhibition, specifically using Y-27632, shows significant promise for treating cochlear synaptopathy.
- This approach offers a potential clinical strategy for addressing sensorineural hearing loss caused by cochlear synaptopathy.
More Related Videos
12:21The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
09:06Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice
Published on: January 9, 2019