Our objective is to find the cause of and a cure for Meniere's disease by developing an animal model and using such a model for treatment. Endolymphatic hydrops, a consistent pathological feature in Meniere's disease, is believed to be due to an increase in endolymphatic pressure and is suspected to cause a sensation of fullness of the ear, tinnitus, dizziness, and hearing loss. Although consistent endolymphatic hydrops can be produced by ablation of the endolymphatic sac in animals, some doubt remains as to whether malfunction of this structure is really the sole cause of Meniere's disease. Because endolymphatic hydrops is shown in other pathological conditions in both human and animals, different etiologies are suspected to produce a similar condition. We will explore the possibility of producing hydrops by other methods. One of our approaches is to apply a slightly higher pressure to the inner ears of normal animals to disturb the homeostasis of inner ear fluids. The pressure, in a magnitude which will cause ischemia of the inner ear, will be applied through the middle ear cavity. The pressure will be an intermittent positive and/or alternating positive and negative pressure which will affect the secretory activity of the stria vascularis, spiral ligament, and vestibular dark cells. Another approach is to administer enzyme inhibitors of secretory cells directly into the inner ear. Based on our own finding that Ca++-ATPase activity in the spiral ligament of the hydropic inner ear is decreased, an inhibitor of this enzyme, vanadate, will be introduced into the normal inner ear. An inhibitor of Na+,K+-ATPase, ouabain, will be infused into the inner ear to affect secretory function of the stria vascularis. Dizziness and the cause of dizziness will be investigated. The middle ear pressure in animals with endolymphatic hydrops will be increased to determine the effect on vestibular symptoms. The theory of the membrane rupture will be tested by rupturing the distended membranous wall by increasing the endolymphatic pressure. With a theory that the vestibular symptoms are not due to rupture of the membranes, osmotic and hydrostatic pressures will be increased by infusion of Ca+ + into the endolymph compartment without rupturing the membranes. For treatment, attempts to decompress endolymphatic hydrops will be made by administering the steroid aldosterone and a potassium-sparing diuretic drug, Dyazide. Gentamicin will be administered into the cistern of the vestibule to affect primarily the vestibular sensory cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000073-37
Application #
2683871
Study Section
Hearing Research Study Section (HAR)
Project Start
1979-04-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
2000-03-31
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
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Shinomori, Y; Kimura, R S (2001) Allopurinol attenuates endolymphatic hydrops in the guinea pig cochlea. ORL J Otorhinolaryngol Relat Spec 63:267-71
Sakikawa, Y; Wall 3rd, C; Kimura, R S (1999) Vestibular responses of normal and hydropic ears of the guinea pig to middle ear pressure application. Ann Otol Rhinol Laryngol 108:271-6
Hamada, M; Kimura, R S (1999) Morphological changes induced by administration of a Na+,K+-ATPase inhibitor in normal and hydropic inner ears of the guinea pig. Acta Otolaryngol 119:778-86
Kimura, R S; Trehey, J A; Hutta, J (1995) Degeneration of vestibular sensory cells caused by ablation of the vestibular aqueduct in the gerbil ear. Ann Otol Rhinol Laryngol 104:155-60
Kikuchi, T; Kimura, R S; Paul, D L et al. (1995) Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat Embryol (Berl) 191:101-18
Ichimiya, I; Adams, J C; Kimura, R S (1994) Changes in immunostaining of cochleas with experimentally induced endolymphatic hydrops. Ann Otol Rhinol Laryngol 103:457-68
Ichimiya, I; Adams, J C; Kimura, R S (1994) Immunolocalization of Na+, K(+)-ATPase, Ca(++)-ATPase, calcium-binding proteins, and carbonic anhydrase in the guinea pig inner ear. Acta Otolaryngol 114:167-76
Kikuchi, T; Adams, J C; Paul, D L et al. (1994) Gap junction systems in the rat vestibular labyrinth: immunohistochemical and ultrastructural analysis. Acta Otolaryngol 114:520-8
Hara, M; Kimura, R S (1993) Morphology of the membrana limitans. Ann Otol Rhinol Laryngol 102:625-30

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