Hearing-Loss Associated Genes Visualized

Researchers from Uppsala University have been able to document and visualize hearing loss-associated genes in the human inner ear, in a unique collaboration study between otosurgeons and geneticists. The findings illustrate subcellular structures in the cochlea involved in the variation of risk of age-related hearing loss in the population. Their findings were published in BMC Medicine.

“The cochlea, and in particular the hearing organ, the organ of Corti, is a highly vulnerable structure that is difficult to analyze since it is surrounded by the hardest bone in the body,” says Helge Rask-Andersen. “We have been able to study some of the molecular components of human hearing that are critical for the conversion of sound to nerve electric impulses.” Genetic variants at 67 genomic regions were found to contribute to an increased risk of age-related hearing loss. Genome-wide association studies (GWAS) on hearing-related traits were performed in the UK Biobank, which has half a million participants from the United Kingdom. Genetic associations are difficult to interpret by themselves and follow-up experiments are often required before causal genes can be inferred.

Candidate proteins from GWAS were visualized with immunofluorescent antibodies and super-resolution structured illumination microscopy. Several proteins were observed within the spiral ganglion, which contains the neuronal cell bodies that innervate the hair cells in the organ of Corti and carry neuronal impulses to the brain via the cochlear nerve. The researchers could also visualize hearing loss-associated proteins in discrete subcellular domains in the hair cells for the first time in humans, such as TRIO and F-actin-binding protein (TRIOBP) in the hair tufts (stereocilia) and LIM domain only protein 7 (LMO7) in the cuticular plate, which is an actin-rich structure that anchors stereocilia to the cell body. The stereocilia are the microscopic or nano-sized ‘hairs’ that protrude from the hair cells of the organ of Corti. They respond to mechanical vibrations from sounds that reach us and are transferred and amplified from the eardrum to the inner ear by the small middle ear bones.

Taken together, the findings from the current study demonstrate that common genetic variations associated with age-related hearing loss affect the structures of the cochlea, in particular the neuronal processes of the spiral ganglion, but also structures directly involved in the transduction of mechanical stimuli to neuronal impulses.