Cochlear structure and function after round window application of ototoxins

Topical round window application of ototoxic agents has been a useful method for studying ototoxicity and hearing loss in the mammalian cochlea. For example, species-specific differences in cochlear susceptibility to damage have been documented using this technique. Carboplatin has been characterized in the literature as a selective inner hair cell (IHC) toxin in chinchillas, while cisplatin has been characterized as a selective outer hair cell (OHC) toxin. The present experiment quantified dose-dependent damage to cochlear hair cells in the chinchilla after a single direct round window application of either cisplatin or carboplatin. Detailed cytocochleograms were obtained for the entire cochlear duct, for a range of doses, along with auditory brainstem response thresholds. In agreement with the literature, although there was variability, at the lowest concentrations tested (2 and 3 mg/ml), carboplatin produced substantial IHC damage with no OHC damage. In contrast, the effects of cisplatin were more variable, and contrary to published reports, across the range of doses producing OHC damage, IHC damage was always observed. Limitations of direct round window ototoxin treatments are discussed, in addition to their potential application in the study of tinnitus.     

Hair cell regeneration after local application of gentamicin at the round window of the cochlea in the pigeon

Hair cells in the basilar papilla of birds have the capacity to regenerate after injury. Methods commonly used to induce cochlear damage are systemic application of ototoxic substances such as aminoglycoside antibiotics or loud sound. Both methods have disadvantages. The systemic application of antibiotics results in damage restricted to the basal 50% of the papilla and has severe side effects on the kidneys. Loud sound damages only small parts of the papilla and is restricted to the short hair cells. The present study was undertaken to determine the effect of local aminoglycoside application on the physiology and morphology of the avian basilar papilla. Collagen sponges loaded with gentamicin were placed at the round window of the cochlea in adult pigeons. The time course of hearing thresholds was determined from auditory brain stem responses elicited with pure tone bursts within a frequency range of 0.35–5.565 kHz. The condition of the basilar papilla was determined from scanning electron micrographs. Five days after application of the collagen sponges loaded with gentamicin severe hearing loss, except for the lowest frequency tested, was observed. Only at the apical 20% of the basilar papilla hair cells were left intact, all other hair cells were missing or damaged. At all frequencies there was little functional recovery until day 13 after implantation. At frequencies above 1 kHz functional recovery occurred at a rate of up to 4 dB/day until day 21, beyond that day recovery continued at a rate below 1 dB/day until day 48 at the 5.6 kHz. Below 1 kHz recovery occurred up to day 22, the recovery rate was below 2 dB/day. A residual hearing loss of about 15–25 dB remained at all frequencies, except for the lowest frequency tested. At day 20 new hair cells were seen on the basilar papilla. At day 48 the hair cells appeared to have recovered fully, except for the orientation of the hair cell bundles. The advantage of the local application of the aminoglycoside drug over systemic application is that it damages almost all hair cells in the basilar papilla and it has no toxic side effects. The damage is more extensive than with systemic application.     

Surgery of the round window

Tympanotomy is routinely performed in our institution to control the round window membrane for patients with recurrent sudden deafness, with Meniere-like attacks, and those with Meniere's disease. In a large number of these patients, especially those with vertigo, perilymph fistula has been diagnosed. Most patients are free of attacks after the fistula has been closed, and in those with a short history of illness, hearing can become normal. In the future, closure of the round window membrane should be considered an important procedure in the treatment of inner ear dysfunctions.     

Immunodefense of the round window

A systematic analysis using serial sectioning of the round window membrane (RWM) in the cynomolgus monkey was performed. Light and transmission electron microscopy (LM and TEM) revealed that the RWM rim may be endowed with gland-like structures with glyco-protein material secernated into the window niche. This was detected in one third of the specimens. The secreted material displayed waste material and scavenger cells. There was also a rich network of capillaries, lymph channels, and sinusoidal veins containing leukocytes. Their abluminal surfaces displayed mature plasma cells and monocytes. These findings suggest that in certain primates the middle ear may have developed specific immunoprotective means for disposal of foreign and noxious substances before they reach the inner ear.     

Stapedectomy and round window closure

Round window closure is an uncommon complication of advanced otosclerosis found in 1% of 30,000 stapedectomy cases. A review of 81 patients representing 110 operation cases was made to determine what factors may alert the otologic surgeon to the patient with round window closure and what factors may identify the patient who will achieve the greatest benefit from stapedectomy.     

Permeability of the round window membrane

Summary Cefmetazole sodium, a cephamycin antibiotic, was shown to pass through the round window membrane into the inner ear of the guinea pig. The concentration of the drug in the inner ear fluid indicated that a larger amount of the drug reached the inner ear through the round window membrane than when administered intraperitoneally.This study was supported by a Research Grant for Specific Diseases from the Ministry of Health and Welfare's Acute Profound Deafness Research Committee of Japan     

Ultrastructure of the round window membrane

The round window membrane presents the only non-osseous wall of the labyrinth. Electron microscopic study of the round window membrane was undertaken in order to determine whether it could act as a route of transmission from the middle to the inner ear. In the cat round window membrane three layers can be identified. The tympanic surface is composed of a single layer of flat cells resting on the basal lamina. Multiple desmosomes and tight cell junctions are present. The intermediate layer contains supporting elements collagen and elastic tissues. The labyrinthine layer is composed of a single layer of long squamous cells which lie end to end on the basal lamina. The absence of intracellular organelles and microvilli, and the lack of basal lamina involutions into the epithelial cells preclude the presence of an active transport mechanism. The tight cell junctions also seem to present a barrier to free diffusion across the membrane. The chemical agents which have been observed to pass from the middle ear into the inner ear may have done so by diffusion through the round window membrane after altering the cell junctions; however, a readily accessible route of transmission through the round window membrane does not appear to be present.     

Blood flow of the round window

Summary Motion pictures of the blood flow of the round window in guinea pigs were taken. In this part the blood flow of the inner ear could be distinguished from that of the middle ear. Our motion pictures show that the blood flow of the inner ear can be observed through the round window membrane without an operation on the inner ear.     

On a novel type of neuron with proposed mechanoreceptor function in the human round window membrane--an immunohistochemical study.

An immunohistochemical study was performed on surgically obtained human fresh cochlear tissue, using synaptophysin antibodies. After immediate aldehyde fixation and decalcification in Na-EDTA serial cryosections were made of the cochlea including the round window membrane (RWM). Apart from highly specific immunostaining of spiral ganglion cells and unmyelinated nerve fibers an immunoreactive neuroreceptor could be demonstrated at the postero-medial insertion of the RWM. The perikaryon showed intense synaptophysin immunoreativity with a distal process projecting into the fibrous stroma of the RWM displaying structural specializations suggestive of a mechanoreceptor function. It is speculated whether the neuroreceptor may be involved in the proprioception and/or mechanoreception of tensile forces generated within the lamina propria during displacement of the yielding RWM in the bony labyrinth. Such a function could be important for the regulation of perilymph pressure.     

Surgical anatomy and pathology of the round window

A study of the surgical anatomy and pathology of the round window was performed on a total of 292 serially sectioned temporal bones. The surgical approach to the round window is discussed with consideration of the anatomical findings. In the pathological study obliteration of the round window niche occurred as a congenital anomaly, in otosclerosis, chronic otitis media and as an end result in suppurative labyrinthitis. Clinical reports seem to indicate that obliteration of the window is associated with a significant hearing loss, contrary to the findings in experimental animals. In chronic otitis media the round window is a pathway for spread of infection to the labyrinth, but also the finding of perilymphatic precipitates adjacent to the window in some ears suggests that certain inflammatory products may enter the scala tympani through the round window and so lead to high tone sensorineural hearing loss.