Apoptosis in the human inner ear. Detection by in situ end-labeling of fragmented DNA and correlation with other markers.

The aim of this study was to obtain baseline data on the recently described special form of single cell death, apoptosis, in normal human inner ears. For this purpose, in situ end-labeling of the fragmented DNA was applied, in conjunction with apoptosis-related markers, to detect cellular elements showing programmed cell death in decalcified and paraffin-embedded tissues. Over 20 specimens were analyzed which were obtained from autopsy cases with no history of acoustic lesions confirmed by histopathology. Based on staining results, we saw no apoptotic signs in the majority of normal adult inner ears. An apoptotic cell captured in the Reissner's membrane of the cochlea from an old patient may, however, indicate an age-related subtle cell loss with the process of apoptosis. Nevertheless, the fact that more apoptosis was not found in our cases suggests that this phenomenon does not contribute significantly to the tissue homeostasis in the adult inner ear under normal conditions. These data are in accordance with our immunohistochemical findings on the p53 nucleoprotein, and proliferating cell nuclear antigen expression since there was no staining in any of the cellular elements, including the mesenchymal cells. This reflects a stationary and stable condition of cells of the vestibular and the cochlear structures, probably to maintain their integrity and the fine sensory functions. As opposed to the above findings, during inner ear development, the epithelial cells lining the cochlear lumen, the ossifying cartilage of the temporal bone, and the mesenchymal cells show different degrees of proliferation in combination with single cell death as signs of maturation of the vestibular and the cochlear apparatus. In addition, apoptosis has been demonstrated in cells of the cochlear stria vascularis from an adult patient treated with high doses of cisplatin, vinblastine and bleomycin prior to death. Furthermore, a wide range of apoptosis could be induced experimentally in a normal ear by an external perfusion of actinomycin D (ActD), which is known to produce programmed cell death in many cell types of different origins. The potential role of cytostatic agents in the apoptotic process of the inner ear needs, however, to be confirmed in large-scale specimens from patients treated with genotoxins. The fact, however, that apoptotic cells are also seen in association with ActD indicates that the fine sensory structure of the cochlea may also be a target for certain chemotherapeutic agents when administered in high doses.