Meniere's disease poses a serious health hazard to affected individuals. Our objective is to identify the cause and devise a cure for this disease by investigations using animal models. Endolymphatic hydrops is a consistent pathological feature in Meniere's disease and animal models. Our studies revolve around investigations of changes in inner ear morphology involved in hydrops formation and evaluation of treatments aimed at reducing hydrops. The endolymphatic sac has been implicated in the cause of hydrops. In some animals, hydrops is simple to develop while in others it is not possible. Therefore, a comparative morphological study including morphometrical and enzyme studies win be conducted on the endolymphatic sacs of different species to elucidate the morphological differences responsible for this variation. We will test the theory that the endolymphadc sac is a secretory organ by destroying the presumed secretory cells and observing the effects on the intraluminal precipitates. The endolymphatic sac may be supplied with sympathetic nerves or other types of nerve fibers and will be investigated with immunohistochemical techniques and electron microscopy. An increase in endolymphatic pressure and membrane rupture are theorized to initiate clinical symptoms for Meniere's disease. A pressure chamber will be utilized to study the effects of pressure increase and decrease on hydropic animals. The membrane rupture theory will also be investigated by rupture of the distended membranes of the animal model or by injection of artificial endolymph into the perilymphatic space, followed by the investigations of neurosensory structures. Development of effective drug therapies to control symptoms of Meniere's disease remains a priority. In animals, aminoglycosides and various non-ototoxic drugs will be administered through the semicircular canal and the cistern of the vestibule to control neural and secretory activities and their effects analyzed. We will investigate hormonal control of endolymphatic hydrops through alteration of the secretory activity of the stria vascularis by administration of B-adrenergic blocking agents. Calcium antagonists will also be given in attempt to decrease the extent of hydrops. The origin of vestibular symptoms in Meniere's disease is not clear. An initial step is undertaken to study, fine morphological changes in the saccula macculi and Scarpa's ganglion cells from the hydropic ears. The state of nerve terminals after sensory cell atrophy will be evaluated by tracer techniques and electron microscopy. The Scarpa's ganglion cells resist retrograde neuronal degeneration whereas the spiral ganglion cells do not. Mitochondrial density in these neurons and their perivascular density will be compared respectively from the series of electron micrograph montages to help elucidate the differences between these ganglia. All these studies will provide insights into understanding the disease process and may help develop better treatments of Meniere's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000073-32
Application #
3215553
Study Section
Hearing Research Study Section (HAR)
Project Start
1979-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
32
Fiscal Year
1993
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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