BREAKDOWN OF THE ROUND WINDOW MEMBRANE-PERMEABILITY BARRIER EVOKED BYSTREPTOLYSIN-O - POSSIBLE ETIOLOGIC ROLE IN DEVELOPMENT OF SENSORINEURAL HEARING-LOSS IN ACUTE OTITIS-MEDIA

Sensorineural hearing loss is a common sequela of acute and chronic ot itis media, and the round window membrane (RWM) is currently being con sidered as a major route for noxious agents to pass from the middle ea r cavity to the cochlea. Streptococcus pneumoniae, a major causative a gent of otitis media, and Streptococcus pyogenes A produce molecularly related toxins, pneumolysin and streptolysin O (SLO), that form large pores in target membranes, In this study, we analyzed the effects of SLO on the permeability of the RWM, Resected RWMs from a total of 104 guinea pigs were embedded between two chambers of an in vitro system, One chamber was designated as the tympanal (cis) compartment, and the other was designated as the inner ear (trans) compartment. The permeab ility of normal and SLO-damaged RWMs towards Na+, [C-14]mannitol, and proteins was Investigated, SLO evoked permeability defects dose depend ently in the RWM with fluxes of both Na+ and [C-14] mannitol being dem onstrable over a time span of up to 8 h. Serum proteins and radioiodin ated SLO were also shown to pass through the damaged RWM. Scanning ele ctron microscopy revealed the morphological correlates to these result s. We propose that damage to the RWM by potent pore-forming cytolysins leads to leakage of ions from the perilymph. Ionic disequilibrium and passage of noxious macromolecules to the cochlea could contribute to disturbances of the inner ear function.