Fish do not lose hearing thanks to retinoic acid

Hair cells are found in the inner ear and are responsible for capturing auditory stimuli and sense of balance. These cells die after acoustic trauma, toxic substances or ageing. Unfortunately, mammals’ hair cells have no regenerative ability, and hence deafness is a common illness among the elderly. Fish, however, are able to regenerate hair cells. Knowing how this capacity to regenerate works leads to new perspectives in the research into treatment of hearing loss.

The Developmental Biology Group of the Department of Experimental and Health Sciences (DCEXS) has discovered that the retinoic acid (RA) pathway triggers the regeneration of damaged hair cells in zebrafish. The results are published in Journal of Neuroscience.

The regenerative properties of retinoic acid have been widely studied in organs such as amphibians’ limbs or heart. However, its regenerative function in the ear of fish remained unknown. By means of genetic and pharmacological inhibition techniques, the team led by Berta Alsina has shown that this acid is essential for cell regeneration in the inner ear of zebrafish. When damaging hair cells, the researchers have seen that the RA pathway is activated, repressing the expression of p27^kip and sox2genes, key compounds in the development of hair cells. This repression allows the generation of new hair cells to reconstruct the damaged sensory organ.

These findings are helpful to understand the molecular mechanisms underlying cell regeneration of non-mammalian vertebrates and point to the retinoic acid pathway as a target in the research into therapeutic agents to recover hearing.

Besides its role in the inner ear, the study shows the regenerative role of retinoic acid in the lateral line of the fish, a sensory organ that allows them to detect the movement of water around them.

Reference work: Davide Rubbini, Àlex Robert-Moreno, Esteban Hoijman, Berta Alsina. Retinoic Acid Signaling Mediates Hair Cell Regeneration by Repressing p27kip and sox2 in Supporting Cells. The Journal of Neuroscience, November 2015. DOI: 10.1523/JNEUROSCI.1099-15.2015