Understanding Hearing Loss Due to Noise Damage Through Changes in Gene Expression


Newswise – An increasing number of people are suffering from hearing loss due to exposure to loud noises from heavy machinery, concerts or explosions. As a result, scientists have worked to understand the mechanism behind how hearing damage actually occurs.

Now, a team led by researchers at the University of Maryland School of Medicine (UMSOM) has released an interactive online atlas representing changes in RNA levels made in different cell types of mouse ears, after damage due to loud noise. These changes in RNA levels are known as changes in “gene expression”.

Once they determined the broader trends in gene expression as a result of the damage, scientists at UMSOM then searched a database of FDA-approved drugs to find which ones are. known to produce opposite patterns to those caused by noise. From this analysis, the research teams identified a handful of drug candidates capable of preventing or treating damage, and ultimately preserving hearing.

Their analysis was published in Cell reports September 28.

“As an otolaryngologist-surgeon-scientist, I see patients with hearing loss due to age or noise damage, and I want to be able to help prevent or even reverse the damage. at their hearing, “said the study manager. Ronna Hertzano, MD, PhD, Professor of otolaryngology-head and neck surgery, anatomy and neurobiology at UMSOM and affiliate member of the Institute of Genome Sciences at UMSOM. “Our in-depth analysis gives us very specific leads to follow in future studies, as well as an encyclopedia that other researchers can use as a resource to study hearing loss.”

The team added their latest data on noise-induced hearing loss to gEAR – Gene expression analysis resource – a tool developed by his laboratory which allows researchers not trained in computer science to browse gene expression data (published earlier this summer).

Dr Hertzano explained that the inner ear resembles the shell of a snail, with separate liquid compartments and sensory cells running its entire length. The ear works like a battery with an ion gradient between the fluid compartments which is generated by the side wall of the shell by adding potassium. Sensory cells detect sound and then communicate with neurons which interact with the brain to interpret the signal. Sensory cells are surrounded by support cells. The inner ear also has resident immune cells to protect it from infection.

Research supervisor Beatrice Milon, PhD, in Dr. Hertzano’s lab first performed an analysis on sensory cells and ear support cells in mice. She collected data on changes in gene expression before and after noise damage. After sharing their study with other researchers in their field, the team heard from scientists at Decibel Therapeutics (led by Joe Burns, PhD) and the Karolinska Institute (led by Barbara Canlon, PhD), who had the data. gene expression from within ear neurons, side wall and immune cells before and after noise damage. The teams then combined the data sets and performed their analysis.

The bioinformatics analyzes were led by Eldad Shulman, MA, MS, of the lab of Ran Elkon, PhD, Tel Aviv University, a bioinformatics expert who has worked in collaboration with Dr Hertzano for over two decades. Together, they harness advanced computer techniques and combine them with biological information to analyze and interpret the data, providing powerful insights to the field of hearing research.

Dr Hertzano says it was so important that they look at a cell-specific level, rather than looking at the entire ear, because they found that most of the gene expression changes were specific to one or two types. cells.

“We expected the subset of neurons generally sensitive to noise and aging to have ‘bad’ changes in genes, so that we could counter them with drugs, but there was no such thing.” said Dr Hertzano. “On the contrary, we have found that the subset of sound trauma resistant neurons activate a program that protects them while highly sensitive neurons have little change in gene expression. We are currently investigating approaches to induce protective changes in noise-sensitive neurons to prevent their loss due to noise and aging.

In another example, the researchers found that only one of the four immune cell types detected had major differences in gene expression.

Additionally, genes related to the immune system have been detected in all types of inner ear cells after noise damage, many of which are controlled by two key regulators.

The research team took overall trends in gene expression and connected them to DrugCentral, a database of known molecular responses to FDA-approved drugs, specifically looking for changes that would be opposite to those that occur. in cells damaged by noise. They identified metformin, a diabetes drug, as a potential candidate, along with certain inhaled anesthetics used in surgery and other drugs.

“Hearing aids and cochlear implants are used to relieve hearing loss, however, there are no therapies available to prevent or treat hearing loss,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and Distinguished Professor John Z. and Akiko K. Bowers, and Dean, UMSOM. “The studies following these findings could eventually lead to drugs to prevent noise-induced occupational hearing loss, for example in factory workers, and to changes in the standardization of anesthesia protocols for surgery. ear, especially in hearing preservation procedures. “

This work was funded by the Eunice Kennedy Shriver National Institute for Child Health and Human Development (R01DC013817, R01DC03544), the Congress-led medical research program of the Department of Defense (MR130240, RH200052), the Carolyn Frenkil Foundation, the Hearing Restoration Project of the Hearing Health Foundation, the Swedish Council for Medical Research and the Hörselforskningsfonden, the Karolinska Institutet, Tysta Skolan and the Office of the Deputy Secretary of Defense for Health Affairs through the Neurosensory and Rehabilitation (W81XWH-16-1-0032), the European Union’s Horizon 2020 Research and Innovation Program (722046, 848261), the United States – Israel Binational Science Foundation (2017218), the Edmond J. Safra Tel Aviv University’s Center for Bioinformatics, Teva Pharmaceutical Industries Ltd, and the Israel National Forum for Bioinnovators.

About University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was established in 1807 as the first public medical school in the United States. It continues today to be one of the world’s fastest growing leading biomedical research companies – with 46 departments, centers, institutes and academic programs, and a faculty of more than 3,000 physicians, scientists. and health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and two-time winner of the Albert E. Lasker Prize in Medical Research. With an operating budget of over $ 1.2 billion, the Faculty of Medicine works closely with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinical care. to nearly 2 million patients each year. The medical school has nearly $ 600 million in extramural funding, with most of its academic departments ranking highly among all medical schools in the country for research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, interns, residents. and fellows. The Combined School of Medicine and the University of Maryland Medicine have an annual budget of more than $ 6 billion and an economic impact of almost $ 20 billion on the state and the local community. The School of Medicine, which ranks 8th among public medical schools in terms of research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-ups. In the last American News and World Report ranking of the best medical schools, published in 2021, the UM School of Medicine is ranked # 9 among 92 public medical schools in the United States and in the top 15 percent (# 27) of the 192 public and private medical schools in the United States. The School of Medicine works locally, nationally and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

About Hector Hedgepeth

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