Researchers at Indiana University School of Medicine are developing new ways to investigate why antibiotics cause permanent hearing loss and hair cell death in humans.
The researchers described how they discovered the autophagy mechanism in hair cells that is connected to the permanent hearing loss caused by aminoglycosides, a family of antibiotics, in a study that was just published in Developmental Cell. The researchers also created one of the first laboratory models that are resistant to hearing loss brought on by aminoglycosides.
According to Bo Zhao, PhD, assistant professor of otolaryngology-head & neck surgery, “this work finds numerous possible treatment targets for reducing hearing loss induced by aminoglycosides.”
One of the primary causes of hearing loss in people is ototoxicity, or hearing loss brought on by drugs. There are more than 48 million hearing-related issues in the US.
For almost a century, serious infections have been treated using aminoglycosides. Due to its low cost and low prevalence of antibiotic resistance, the medication is the first-line treatment for life-threatening infections, particularly in developing nations. However, it has been reported that in 20-47% of patients, it causes the death of hair cells, which leads to permanent hearing loss. The underlying mechanisms are unclear. In the inner ear, hair cells are in charge of sound reception.
Zhao employed biochemical screening to find proteins present in hair cells. Zhao’s lab studies the molecular pathways causing hearing loss. They initially found that aminoglycosides bind to the RIPOR2 protein, which is important for hearing.
We think that RIPOR2 is necessary for aminoglycoside-induced hair cell death since aminoglycosides specifically cause a fast localization change of RIPOR2 in hair cells, according to Zhao.
In the lab, the researchers created a mouse with normal hearing but drastically reduced RIPOR2 expression. Zhao claimed that after receiving treatment with aminoglycosides, the model neither had severe hair cell death nor hearing loss.
“The autophagy mechanism in hair cells is then regulated by RIPOR2, we later learned. Knowing this, we created other laboratory mice that did not express a number of essential autophagy proteins and did not experience hearing loss or hair cell death when exposed to the antibiotic “According to Jinan Li, PhD, a postdoctoral fellow in the Zhao lab and the paper’s first author.
According to the study’s authors, future research may employ the proteins discovered in this study as therapeutic targets to prevent hearing loss brought on by aminoglycosides.
The article’s authors also include Ulrich Mueller, PhD, Bloomberg Distinguished Professor of Neuroscience and Biology at Johns Hopkins University, Chang Liu, PhD, a postdoctoral fellow in the Zhao group, and Zhao and Li. The National Institutes of Health and Indiana University School of Medicine funded the study.
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