New findings help explain hearing loss

New findings help explain hearing loss

BY SHAWN HUTCHINS
Special to the Rice News

Robert Raphael’s research into the molecular biophysical basis of hearing is producing a wave of insight into the causes of hearing loss and deafness. The T. N. Law Assistant Professor of Bioengineering, Raphael investigates the intricate inner workings of the human auditory system.

How auditory membrane cells orchestrate the detection and decoding of sounds is largely unclear to scientists. Raphael and his Membrane and Auditory Bioengineering Group are investigating the regulation of ion homeostasis in the inner ear by membrane transporters and the intermolecular interactions of prestin.

ROB RAPHAEL AND IMRAN QURAISHI

Prestin, a unique membrane protein found in the outer hair cells of the cochlea, transforms electrical energy into mechanical energy and powers the outer hair cells that provide cochlea amplification. Recently, Raphael demonstrated that alterations in the membrane microenvironment alter prestin’s function, which could be important to understanding many diseases that cause deafness.

To function, prestin needs energy generated by a specialized tissue in the cochlea called the stria vascularis. To study this process, Raphael and graduate student Imran Quraishi constructed a mathematical model of potassium transport into the endolymph by the outer layer of cells of the stria vascularis. The model predicts normal tissue function and explains why several inherited forms of genetic deafness cause cochlear malfunction. The results were published earlier this year in the American Journal of Physiology.

Since then, the model was extended and now accounts for the generation of the endocochlear potential by the second layer of cells in the stria vascularis. With a complete in silico model, the group will begin experiments to test potential drug therapies for hearing loss.

Raphael also uses optical imaging techniques to study the molecular mechanisms associated with prestin function, the potential of ototoxicity from nonsteroidal anti-inflammatory agents (NSAIDs) and reactive oxygen species.

The group is applying fluorescence resonance energy transfer (FRET), confocal
microscopy and other advanced optical imaging techniques. These studies also have implications for noise-induced hearing loss and cochlea dysfunction
and damage. The application of the new methods will lay a foundation for assessing whether antioxidants can prevent the deleterious actions of these compounds.

”It has been known for quite some time that aspirin and other nonsteroidal anti-inflammatory agents cause hearing loss and tinnitus, but we’ve discovered aspirin-like molecules alter membrane mechanics in model systems and have begun to demonstrate they also change the nanoscale curvature of the outer hair cell membrane,” said Rafael.

Raphael’s group is supported by grants from the Deafness Research Foundation, the National Institute on Deafness and Other Communication Disorders and the National Organization for Hearing Research.