DIFFUSIBLE FACTORS REGULATE HAIR CELL REGENERATION IN THE AVIAN INNER-EAR

Damage to the avian inner ear results in up-regulation of mitotic acti vity resulting in regeneration of hair cells. The objective of this in vestigation was to determine whether the damaged inner ear epithelium releases a soluble mitogen that is responsible for the up-regulation o f proliferation. The sensory epithelium from normal and drug damaged a vian inner ears was cultured alone or in the presence of other culture s. As previously shown in vivo and in vitro, damaged organs displayed increased supporting cell proliferation compared with undamaged organs , leading to eventual morphologic and functional recovery. When damage d organs were cocultured with an undamaged organ, proliferation was in creased in the undamaged tissue. When undamaged organs were cultured t ogether, proliferation was decreased. These results indicate that a so luble factor released from the damaged inner ear epithelium stimulates proliferation and suggest the release of a factor from normal tissue that suppresses mitotic activity. Thus, reparative hair cell regenerat ion in the inner ear appears to be regulated by a balance between prol iferative and antiproliferative paracrine factors.