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.
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