The histopathologic findings of increased thickness of the vascular walls of the modiolar arteries and stria vascularis, increased strial atrophy, and decreased number of strial vessels may have led to decreased cochlear microcirculation. Deficiency in the circulation and perfusion of the cochlea may be a factor in presbycusis.

ObjectiveWe aimed to elucidate the ossification process of the otic capsule in postnatal C57BL/6 mice and depict the three‐dimensional (3D) process of otoconial mineralization in vivo.MethodsThe otic capsules of C57BL/6 mice were stained with alizarin red and imaged/compared using micro‐computed tomography on postnatal day (P) between P0 and P8, P10, P15, and P30 and 3–4 months old (P3–4Mo). We reconstructed 3D images of the otic capsule and otoconia and measured the bone mineral density using x‐ray absorptiometry on each age.ResultsThe 3D reconstructed otic capsule images revealed two ossification centers of the otic capsule at P0. One was observed around the ampulla of the superior semicircular canal and utricle, and the other was observed around the ampulla of the posterior semicircular canal. The cross‐sectional views demonstrated that modiolar ossification developed from the base to the apex from P4 to P8. The inter‐scalar septum ossified bidirectionally from the modiolus and bony otic capsule from P8 to P15. The mineralized otoconia were first detected in the utricle at P3 and saccular otoconia at P6. The density of the utricle and saccular otoconia showed different growth trends.ConclusionTo the best of our knowledge, this is the first study to demonstrate the 3D appearance of the otic capsule and otoconia in different developmental stages of mice. We also revealed that modiolar and inter‐scalar septal calcification is the final event in the cochlea and that it can be susceptible to pathological conditions (cochlear congenital malformations and hereditary vestibular diseases). The unique features of the ossification process and duration may explain these pathological conditions observed in humans.Level of Evidence3

Tissue-resident macrophages play an important role in clearance, development, and regulation of metabolism. They also function as sentinel immune cells, initiating inflammatory responses, clearing inflammatory debris, and maintaining homeostatic tissue environment. In the cochlea, the roles of tissue-resident macrophages include maintaining steady-state tissues, immunological defense, and repairing pathological conditions associated with noise, ototoxic drugs, aging, and various pathogens. Perivascular macrophages (PVMs) are a unique subset of tissue-resident macrophages that are closely associated with blood vessels and have unique expression markers in certain tissues. PVMs are found in the inner ear, brain, skin, liver, and retina. The origin of PVMs in the inner ear is unclear, but they are already present during embryonic development. PVMs are members of the blood labyrinth barrier and regulate blood vessel permeability in the stria vascularis, which lies on the lateral wall of the cochlear duct and is crucial for endocochlear potential formation. The cytoplasm of strial PVMs can contain pigment granules that increase in number with age. Strial PVMs are activated by the loss of Slc26a4 in the cochleae, and they subsequently phagocytose aggregated pigment granules and possibly degenerated intermediate cells. This review summarizes the current knowledge of characteristic features and proposed roles of PVMs in the stria vascularis. We also address macrophage activation and involvement of pigment granules with the loss of Slc26a4 in the cochleae.

Objective Although prolonged use of antibiotics is very common in cystic fibrosis (CF) patients, no studies have assessed the changes in both cochlear and peripheral vestibular systems in this population. Methods We used human temporal bones to analyze the density of vestibular dark, transitional, and hair cells in specimens from CF patients who were exposed to several types of antibiotics, as compared with specimens from an age-matched control group with no history of ear disease or antibiotic use. Additionally, we analyzed the changes in the elements of the cochlea (hair cells, spiral ganglion neurons, and the area of the stria vascularis). Data was gathered using differential interference contrast microscopy and light microscopy. Results In the CF group, 83% of patients were exposed to some ototoxic drugs, such as aminoglycosides. As compared with the control group, the density of both type I and type II vestibular hair cells was significantly lower in all structures analyzed; the number of dark cells was significantly lower in the lateral and posterior semicircular canals. We noted a trend toward a lower number of both inner and outer cochlear hair cells at all turns of the cochlea. The number of spiral ganglion neurons in Rosenthal’s canal at the apical turn of the cochlea was significantly lower; furthermore, the area of the stria vascularis at the apical turn of the cochlea was significantly smaller. Conclusions Deterioration of cochlear and vestibular structures in CF patients might be related to their exposure to ototoxic antibiotics. Well-designed case-control studies are necessary to rule out the effect of CF itself.