A New Strategy to Detect Cochlear Damage and Promote Spiral Ganglia Neural Regeneration
Abstract
We are living in a world that is noisier than ever before. Consequently, anyone can be inflicted with noise-induced hearing loss. In fact, more than 30 million Americans are suffering from some degree of hearing loss. The onset of hearing impairment and its severity is exceptionally high among military Service Members and Veterans due to service-related noise exposure. Noise exposure causes both loss of outer hair cells (OHCs) and synapses between inner hair cells (IHC) and spiral ganglion neurons (SGN). OHC is the biological amplifier that gives us enormous sensitivity and capability to obtain specific signals from a noisy environment. At the same time, SGNs are the essential components that transport sound information to the brain. There is no effective method to recover lost OHCs and SGNs. It has also been recognized that a growing population, including many U.S. Service Members, suffer from difficulty hearing in a noisy environment despite having normal hearing tests. This phenomenon is called hidden hearing loss. In many of these cases, people do not even realize they have hearing loss or hidden hearing loss until symptoms worsen. However, we do not have a method to detect or treat hidden hearing loss noninvasively. Current methods for hearing loss detection do not reliably detect low level cochlear damage. Most importantly , it is impossible to identify cochlear stress before irreversible tissue damage and hearing loss have already occurred. Thus, an effective method for detecting cochlear stress is urgently needed. It is well known that OHCs are the first cells in the hearing organ to die after intensive noise exposure. Despite extensive efforts, we still do not have an effective method to protect OHCs as we do not fully understand why OHCs are so sensitive to various assaults. Because noise exposure causes excess calcium ions to accumulate inside OHCs, which can lead to OHC loss, we will investigate the OHC-specific calcium-binding protein known as oncomodulin. OHCs have an extraordinarily high concentration of oncomodulin. Recently, several papers showed that the damaged nerves in the eye could trigger an inflammatory response that leads neutrophils and macrophages to transiently release oncomodulin, which then promotes optical nerve regeneration/survival. This discovery inspires us to suspect that oncomodulin in the OHCs may also have a similar function to protect SGNs in the ear. We hypothesize that OHCs may act as a standby savior that can release oncomodulin whenever cochleae are assaulted. Consequently, the released oncomodulin diffuses to nearby synaptic connection areas to stimulate the regrowth or survival of SGNs, just as oncomodulin does in the eye. Therefore, the objective for this proposal is twofold: (1) To verify if oncomodulin is released from OHCs under moderate noise exposure and determine whether oncomodulin could be used as a serum biomarker to detect cochlea damage. (2) To determine whether oncomodulin has the neurotrophic capability to repair damaged SGNs. In the hearing research field, oncomodulin is widely believed to be a calcium buffer protein essential for OHC survival. Oncomodulin is a cytoplasmic protein that typically stays in OHCs. Suppose oncomodulin secretion from OHCs is regulated by noise intensities as we predict. In that case, oncomodulin is likely circulated into the bloodstream, which can be used as a serum biomarker for detecting cochlea damage. Since oncomodulin is only expressed in OHCs and a few other cells, oncomodulin could be a very specific marker for indicating hearing impairment. The knowledge obtained from the proposal will allow us to establish a noninvasive method to detect cochlear stress and damages caused by moderate noise exposure, which is an urgent need to prevent and treat hearing impairment. In addition, oncomodulin has never been considered as a neurotrophic factor in the hearing research field. The fact that oncomod
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310730
Entities
People
- Jing Zheng
Organizations
- Northwestern University
- United States Army