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Abstract
Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, frequently caused by noise trauma and aging, with inflammation being implicated in both pathologies. Here, we provide the first direct measurements of proinflammatory cytokines in inner ear fluid, perilymph, of adolescent and 2-year-old mice. The perilymph of adolescent mice exposed to the noise intensity resulting in permanent auditory threshold elevations had significantly increased levels of IL-6, TNF-α, and CXCL1 6 h after exposure, with CXCL1 levels being most elevated (19.3 ± 6.2 fold). We next provide the first immunohistochemical localization of CXCL1 in specific cochlear supporting cells, and its presumed receptor, Duffy antigen receptor for chemokines (DARC), in hair cells and spiral ganglion neurons. Our results demonstrate the feasibility of molecular diagnostics of SNHL using only 0.5 μL of perilymph, and motivate future sub-μL based diagnostics of human SNHL based on liquid biopsy of the inner ear to guide therapy, promote hearing protection, and monitor response to treatment.
Highlights
Sensorineural hearing loss (SNHL) is the most common sensory deficit in the world
We focus on proinflammatory cytokines because they play an important role in a plethora of diseases [13], and are thought to be important mediators of numerous middle and inner ear maladies [14,15,16,17], including noise-induced hearing loss [18,19,20,21]
Compared to the perilymph of unexposed animals (N = 19 ears), perilymph collected 6 h after exposing mice to noise levels that resulted in PTS (103 dB sound pressure level (SPL) at 8–16 kHz for 2 h) (N = 17 ears) demonstrated a statistically significant elevation of the levels of proinflammatory cytokines CXCL1, IL-6, and TNF-α (vPLF: 56.2 ± 4.9 re 28.6 ± 2.7 pg/mL, p < 0.0001 (Figure 1)
Summary
Sensorineural hearing loss (SNHL) is the most common sensory deficit in the world. Disabling SNHL currently affects nearly half a billion people [1], and its incidence increases with age, affecting 16% of people aged 18 years and older, 34% of people aged 65–69 years, and 72% of people aged 85–90 years [2, 3]. In addition to being economically costly to society, with the annual cost of unaddressed hearing loss being $750 billion globally [4], SNHL is physically and emotionally costly to individuals, as it is associated with cognitive dysfunction, dementia, and depression [5]. Despite these staggering statistics, the cellular basis of human SNHL is typically unknown in living people because the inner ear cannot be biopsied today and its cells cannot be imaged clinically [6, 7]. There is a potential to overcome these barriers by performing liquid biopsy of the inner ear based on sampling of its fluid, perilymph, which bathes the vast majority of inner ear cells
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