The Key to age-related hearing loss
An international team of researchers led by Associate Professor Ronna Hertzano from the University of Maryland has identified the Ikzf2 gene, which acts as a key regulator of the activity of the outer hair cells of the inner ear, necessary for sound recognition.
The inner ear has two types of sensitive hair cells needed to register sounds. Internal hair cells convert sounds into nerve signals that subsequently enter the brain. In contrast, external hair cells amplify and regulate sounds. Without them, the sounds become muffled, and the internal hair cells send a very weak signal to the brain.
The loss of external hair cells is the cause of the age-related hearing loss that occurs in all people without exception. Some of these cells, which provide the recognition of high-pitched sounds, are lost already at the age of 30. By itself, exposure to sounds, especially loud ones, eventually leads to damage to the external hair cells.
Dr. Herzano's group used bioinformatics and functional genomics approaches to identify a gene that plays a key role in regulating the activity of genes involved in the development of external hair cells. In the course of the work, the scientists joined forces with researchers from the Harwell Institute (Great Britain), working under the guidance of Dr. Michael Bowl, who identified mice with early progressive hearing loss, the cause of which is a violation of the functioning of external hair cells. The reason for the association was to find out that both groups were studying the same gene. The subsequent joint work was devoted to elucidating the biological function of the Ikzf2 gene encoding the helios transcription factor, as well as its role in the development of external hair cells. (Transcription factor is a protein that regulates gene expression.) The mutation of the mouse version of the Ikzf2 gene studied by the authors changed one amino acid in a critical part of the helios molecule, which disrupted the transcriptional regulatory activity of this protein.
To test the assumption that helios is necessary for the differentiation of external hair cells, the researchers injected a viral vector into the internal hair cells of newborn mice that triggers helios overexpression. As a result, some of the mature internal hair cells acquired the characteristics of external hair cells. In particular, internal hair cells with overexpression of the helios protein began to produce the protein prestin and demonstrate the ability to electrical mobility inherent exclusively in these cells. Thus, the ability of the helios transcription factor to endow internal hair cells with characteristic features of external hair cells was demonstrated.
According to the director of the Harwell Institute, Professor Steve Brown, the development of methods for the treatment of age-related hearing loss is one of the most difficult tasks facing medical and biomedical science. Understanding the genetic programs underlying the development and maturation of the inner ear hair cells processing and transmitting sound signals is a prerequisite for the emergence of approaches to the regeneration of these cells, massively dying with age-related hearing loss. By identifying the key regulator of Ikzf2/helios of the maturation process of external hair cells, the authors shed light on this program. Now researchers have a target at their disposal, by influencing which it is theoretically possible to induce the production of new external hair cells in the damaged inner ear, which brings us one step closer to the appearance of methods for treating age-related hearing loss.
Article by Lauren Chessum et al. Helios is a key transcriptional regulator of outer hair cell maturation published in the journal Nature.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru Based on University of Maryland School of Medicine: UMSOM Expert Discovers Key Gene in Cells Associated with Age-Related Hearing Loss.