microRNAs have a role in hearing impairment

Alice McCarthy, September 23rd, 2010 | Filed under
  • Scanning electron microscopy image of an inner ear
    outer hair cell from a mouse lacking microRNAs.

    Image courtesy of Amiel Dror, Tel Aviv University

The human inner ear is surprisingly complex, controlled by a large variety of genes – most with unknown roles – that can influence hearing loss. To identify the genetic influences leading to hearing loss, Prof. Karen B. Avraham, of the Department of Human Molecular Genetics and Biochemistry at Tel Aviv University, Israel is investigating the biological roles of a group of non-coding RNAs called microRNAs (miRNAs). These RNA molecules are involved in turning off, or silencing, specific genes. During her career, Professor Avraham has been involved in the discovery of ten genes associated with hearing impairment, including a form of deafness with blindness, Usher syndrome.

“There is extreme clinical and genetic heterogeneity in hearing loss,” Avraham said during a talk given on Thursday to the Broad community. For the approximate 28 million Americans with hearing loss, this complexity of genes explains the wide range of hearing loss, from mild loss to profound deafness at birth. These genes also explain non-syndromic loss, where hearing loss is an isolated finding, as well as more than 400 syndromes, including Usher Syndrome with retinoma pigmentosa, where hearing impairment is just one of several manifestations.

Researchers know that approximately 30-50% of hearing loss cases stem from defects, or mutations, in the connexin-26 gene, depending on patients' geographic origins. But the genetic basis of the remaining 50-70% of cases is unknown.

For these reasons, revealing the genetic mechanisms underlying hearing loss is essential to discover new therapeutic options for those seeking them.

For the past four years, Professor Avraham and her colleagues having been researching miRNAs to identify and study their targets. miRNAs are essential for the development and function of the ~16,000 human inner ear hair cells that are responsible for capturing sound and transmitting it to the auditory nerves. However, miRNA target identification and validation has hardly been broached in research efforts. “We want to know the targets of these miRNAs, a finding that is crucial for understanding gene expression and regulation in the inner ear,” says Karen Avraham.

By analyzing neuroepithelial tissue (as opposed to whole inner ear tissue), Karen Avraham’s team identified 53 miRNAs that are differentially seen in the cochlea and vestibule, the two main components of the inner ear responsible for hearing and balance, respectively. Her current work is focused on discovering specific miRNA-target pairs to help identify pathways that are involved in inner ear cell development, survival, and protection against stress. Avraham told those in attendance at her talk that “the targets identified that influence differences in inner ear cell survival and regeneration may help lead toward development of therapeutic approaches for hearing loss.” For those suffering from hearing loss, or at risk for it later in life, let’s hope she and her colleagues make rapid progress.