MACROMOLECULES OF COCHLEAR NONSENSORY TISSUES, & FLUIDS

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It is the general objective of this proposal to study the macromolecular makeup of the accessory structures bounding the cochlear duct - the tectorial and basilar membranes, spiral ligament, and spiral limbus - and the respective fluids in the mammal, and of the tectorial and basilar membranes in the bird. Of the fluids, endolymph will be given special attention. The macromolecules studied are collagens, proteoglycans, and glycoproteins, which form the major structural elements of the extracellular matrix of connective tissue. Interactions between these macromolecules in tissues and surrounding fluids determine their specific and unique properties. The sampling technique permits isolation of discrete cochlear structures and uncontaminated inner ear fluids. Highly sensitive biochemical and immunochemical techniques (including two-dimensional gel electrophoresis and amino acid sequencing) will be used, and molecular biologic in vitro and in situ studies will be conducted. The biochemical and molecular biologic features of these unique tissues, integrated with existing structural and biophysical knowledge, will provide better understanding of cochlear biomechanics, and will give insight into the processes involved in regeneration of avian hair cells and supporting structures. Most studies on auditory function treat the inner ear as a purely physical system; however, the effectors of the mechanical processes are living cells, and biochemical changes are the basis of the majority of pathological conditions. Genetic disorders of collagen metabolism (e.g. osteogenesis imperfecta, Marfan's syndrome, and Alport's syndrome) and glycosaminoglycans (mucopolysaccharidoses such as Hurler's syndrome and Hunter's syndrome) all result in impairment of auditory function. It is readily conceivable that the tectorial and/or basilar membranes, which both consist primarily of collagen and glycosaminoglycans, are involved in these disorders. In addition, changes of connective tissue occurring with age could be one of the dysfunctions involved in presbycusis.