We utilized electron and immuno-fluorescent microscopy to examine cytoskeletal structures of cochlear outer hair cells in control and Ames waltzer 3J (av3J) mice, to investigate the mechanism of stereocilia bundle polarity established in mature hair cells. The Ames waltzer mouse harbors a mutation in the protocadherin 15 gene (Pcdh15) and is a model for deafness in Usher syndrome 1F and non-syndromic deafness DFNB23. We examined dynamic ultrastructural changes of the fonticulus, kinocilia and basal body/centriole complex during initiation of bundle organization, between embryonic day 16.5 (E16.5) and postnatal day 10 (P10). In normal controls, maturation of stereocilia bundle started around E18, with the earliest changes in kinocilia lateralized to the side of the cell, prior to cuticular plate formation and stereocilia elongation. In av mice, stereocilia bundle disorganization first appears at E18 and increased after P0, with mislocalization of the kinocilium and the fonticulus. These observations support the hypothesis that organization of stereocilia and cell polarization may be dependent on proper orientation of structural components in the apical portion of the cell during development.
Recently, a number of clinical studies for cell therapy have been reported and clinically used for several intractable diseases. Inner ear cell therapy for sensorineural hearing loss also has been studied using some laboratory animals, although the successful reports for the hearing recovery were still few. Cochlear fibrocytes play important roles in normal hearing as well as in several types of sensorineural hearing loss due to inner ear homeostasis disorders. Recently, we developed a novel rat model of acute sensorineural hearing loss due to fibrocyte dysfunction induced by a mitochondrial toxin1), 2). In this model, we demonstrate active regeneration of the cochlear fibrocytes after severe focal apoptosis without any changes in the organ of Corti. To rescue the residual hearing loss, we transplanted mesenchymal stem cells into the lateral semicircular canal; a number of these stem cells were then detected in the injured area in the lateral wall. Rats with transplanted mesenchymal stem cells in the lateral wall demonstrated a significantly higher hearing recovery ratio than controls. The mesenchymal stem cells in the lateral wall also showed connexin 26 and connexin 30 immunostaining reminiscent of gap junctions between neighboring cells3). These results indicate that reorganization of the cochlear fibrocytes leads to hearing recovery after acute sensorineural hearing loss in this model and suggest that mesenchymal stem cell transplantation into the inner ear may be a promising therapy for patients with sensorineural hearing loss due to degeneration of cochlear fibrocytes.
The advantages and limitations of the microscope have defined transmastoid access as the surgical intervention of choice for the treatment of cholesteatoma. The wideangle view provided by the endoscope enables transcanal access to the tympanic cavity and its otherwise difficult-to-reach extensions: the attic, sinus tympani, facial recess, and hypotympanum. These areas are the primary sites of disease and surgical failure to cure. This report is a summary of the author's two 17 years of experience with the use of transcanal operative endoscopy as the primary approach to the management of cholesteatoma.