The overall goal of this research is to improve our understanding of inner ear function by improving our knowledge of its molecular composition. Specifically, we will continue and extend our investigation of inner ear glycoconjugates (GCs) using cationic dyes, immunohistochemistry, and biochemical assays of inner ear proteins. Our general hypothesis is that the inner ear consists of numerous and varied GCs that serve a number of important functions such as structural, adhesive, trophic, cell-membrane receptors, ion channels, and electrostatic charge boundaries. Using cationic dyes that preserve GCs, the distribution of these macromolecules will be investigated using transmission and scanning electron microscopy. Our focus will be those GCs that appear to attach the stereocilia to one another and to the tectorial membrane. Alteration of these macromolecules would have a deleterious effect on hearing if they are responsible for the mechanical coupling of the hair cells to the tectorial membrane. In order to identify these and other inner ear GCs, we will use antibodies to the integrin family of adhesive glycoproteins and a Na + -Ca + + exchange protein. Integrins provide important adhesive functions between cell-to- cell and cell-to-matrix contacts in other tissues. Preliminary results with the exchange protein antibodies suggest that it is localized to the two main ion transporting tissues of the inner ear: stria vascularis and the dark cells in vestibular tissues. This research will also investigate the potential neuroprotective effects exogenous gangliosides have on ototoxic drug administration and acoustic trauma. Furthermore, this research will biochemically and immunohistochemically identify autoantibodies in human sera that may be responsible for inner ear disorders in patients with idiopathic hearing loss, Systemic Lupus Erythematosus, and Rheumatoid Arthritis. By improving our understanding of the molecular composition of the inner ear, we will not only improve our understanding of normal hearing but also obtain better diagnostic criteria for certain diseases and be able to suggest more specific treatment.
