MACROMOLECULES OF COCHLEAR NONSENSORY TISSUES, & FLUIDS

本提案的总体目标是研究大分子 构成耳蜗管的附属结构- 顶盖和基底膜、螺旋韧带和螺旋利姆布斯-和 哺乳动物体内的相应液体，以及顶盖和基底动脉的液体， 鸟类的膜。 在这些液体中，内淋巴将被赋予特殊的 关注 研究的大分子是胶原蛋白，蛋白聚糖， 糖蛋白，其形成的主要结构要素， 结缔组织的细胞外基质。 这些之间的相互作用 组织和周围液体中的大分子决定其特异性 和独特的属性。 采样技术允许分离离散耳蜗结构 和未受污染的内耳液 高度敏感的生化和 免疫化学技术（包括双向凝胶电泳 和氨基酸测序），以及体外分子生物学 并进行实地研究。 这些独特组织的生化和分子生物学特征， 结合现有的结构和生物物理知识， 提供更好的理解耳蜗生物力学，并将给予 深入了解鸟类毛细胞再生过程 和支撑结构。 大多数关于听觉功能的研究都将内耳视为一个纯粹的 物理系统;然而，机械过程的效应器是 活细胞和生物化学变化是大多数人的基础。 病理条件。 胶原代谢的遗传性疾病（例如， 成骨不全、马凡氏综合征和Alport氏综合征）， 糖胺聚糖（粘多糖沉积症，如Hurler综合征和 亨特氏综合征）都导致听觉功能受损。 是 很容易想象， 两者都主要由胶原蛋白和糖胺聚糖组成， 在这些疾病中。 此外，结缔组织发生变化， 可能是老年性耳聋的功能障碍之一。

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.