Aminoglycoside Increases Permeability of Osseous Spiral Laminae of Cochlea by Interrupting MMP-2 and MMP-9 Balance

Abstract

The spiral ganglion neurons (SGNs) located in the Rosenthal's canal of cochlea are essential target for cochlear implant. Previous studies found that the canaliculi perforantes, small pores on the surface of the osseous spiral lamina (OSL) of the scala tympanic (ST) of cochlea, may provide communication between the cochlear perilymph and SGNs. In this study, we found that chronic treatment of aminoglycosides antibiotics, which is well known to cause sensory cell damage in the cochlea, induced significant damage of bone lining cells on the OSLs and increased the permeability of the Rosenthal's canal. The pores among the bone lining cells became significantly wider after chronic treatment of amikacin (100 mg/kg/day for 3-7 days). Injection of Evans Blue in the ST resulted in significant increase in its migration in the modulus in the amikacin-treated cochlea compared to the control ears, suggesting increased permeability of these passages. Treatment of amikacin with oxytetracycline, an inhibitor of matrix metalloproteases (MMPs), significantly reduced the amount of dye migrated from the ST to the modiolus. These results suggest that amikacin enhanced the permeability between the ST and SGNs by increasing MMPs. Aggregating the permeability of the bone lining cells on the OSLs may benefit gene and stem cell delivery to the SGNs in the cochlea.

A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens

“…Expression of MMP2 in the cytosol of type I spiral ganglion neuron was consistent with imaging in the rat spiral ganglion [73,112]. We are also able to report expression of MMP2 in the outer spiral bundle.…”

“…MMP2 is a matrix metalloproteinase that degrades type IV collagen, which may play a role in the elongation of neuronal outgrowths during development and extracellular matrix remodeling after tissue damage. Several experiments in guinea pig and rat models for cochlear damage have demonstrated that that Mmp2 RNA expression increases after noise exposure [71], ototoxic aminoglycoside antibiotics [73,112], and cochlear implantation [72]. Aminoglycosides also increased the permeability of the osseous spiral lamina in rat cochlea, which led to increased diffusion across canaliculi perforantes from the scala tympani and scala vestibuli to spiral ganglion neurons embedded in Rosenthal's canal [73].…”

“…Several experiments in guinea pig and rat models for cochlear damage have demonstrated that that Mmp2 RNA expression increases after noise exposure [71], ototoxic aminoglycoside antibiotics [73,112], and cochlear implantation [72]. Aminoglycosides also increased the permeability of the osseous spiral lamina in rat cochlea, which led to increased diffusion across canaliculi perforantes from the scala tympani and scala vestibuli to spiral ganglion neurons embedded in Rosenthal's canal [73]. This effect was attenuated by concomitant administration of the metalloproteinase inhibitor oxytetracycline [73].…”

Cochlear-Bioelectrode: Auditory response to cochlear implant can be improved by stem cell delivery into inner ear in a pig model

“…Previous studies have con rmed that naturally existing tiny openings in the osseous spiral lamina (OSL) provide communication for dyes and neural growth factors to move between the scala tympani (ST) and the cochlear modiolus where sit the SGNs. Due to the small diameter of these openings (2-20 um), only a single cell can pass through (9). When transplanted to the ST, stem cells will congregate and are unable to pass through the pores as single cells.…”

Mitochondrial tRNAIle A4317G mutation may be associated with hearing impairment in a Han Chinese family

“…It has been estimated that ≥50% of cases of congenital deafness have genetic causes. At present, the etiology of hearing loss remains largely unknown, although gene alterations (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and environmental factors, including aminoglycoside antibiotics (AmAn), are now generally considered to be involved in this condition (16).…”