Breakdown of the round window membrane permeability barrier evoked by streptolysin O: possible etiologic role in development of sensorineural hearing loss in acute otitis media

Abstract

Sensorineural hearing loss is a common sequela of acute and chronic otitis media, and the round window membrane (RWM) is currently being considered as a major route for noxious agents to pass from the middle ear cavity to the cochlea. Streptococcus pneumoniae, a major causative agent 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 permeability of normal and SLO-damaged RWMs towards Na ؉ , [ 14 C]mannitol, and proteins was investigated. SLO evoked permeability defects dose dependently in the RWM with fluxes of both Na ؉ and [ 14 C]mannitol being demonstrable over a time span of up to 8 h. Serum proteins and radioiodinated SLO were also shown to pass through the damaged RWM. Scanning electron microscopy revealed the morphological correlates to these results. 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.

Bacterial Cytolysin Perturbs Round Window Membrane Permeability Barrier In Vivo: Possible Cause of Sensorineural Hearing Loss in Acute Otitis Media

“…The present results indicate that the passage of cytolysins such as SLO or pneumolysin themselves would not be expected to contribute to disturbances of inner-ear function, because the toxins probably will become quantitatively entrapped in the middle ear due to their binding to cells lining this cavity. In the in vitro system used previously (10), the entire epithelial lining of the middle ear was absent, and the RWM alone may have been unable to trap all of the tracer, leading to the deviant finding compared to that of the present study. Thus, SLO could become a tool to transiently permeabilize the RWM, making possible the introduction of various agents into the inner ear.…”

“…When the RWM surrounded by an intact bony frame was excised and embedded in a Plexiglas sheet separating two buffer chambers, low concentrations of SLO provoked rapid breakdown of the RWM permeability barrier. Fluxes of Na ϩ , [ 14 C]mannitol, serum proteins, and radioiodinated SLO were demonstrable (10).…”

Role of Mannitol in Reducing Postischemic Changes in Distortion‐Product Otoacoustic Emissions (DPOAEs): A Rabbit Model

“… 16,36 In vitro, mannitol appeared not to pass through the RW membrane unless combined with streptolysin O. 40 Evidence from our and other in vivo studies suggest that mannitol does cross the RW in pharmacologically sufficient quantities. 4,7 …”

Nanoparticle-based drug delivery in the inner ear: current challenges, limitations and opportunities

“…Permeability of the RWM can also be affected by inflammatory disease processes such as otitis media due to the scarring and fibrosis of granulation tissue hindering transport [49]. Attempts have been made to increase membrane permeability and porosity using agents such as O-streptolysin [50]. However, it is difficult to attain uniform drug distribution throughout the cochlea.…”