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Role of macrophage migration inhibitory factor in age-related hearing loss
1Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Abstract:
Hearing loss related to aging is the most common sensory disorder among elderly individuals. Macrophage migration inhibitory factor (MIF) is a multi-functional molecule. The aim of this study was to identify the role of MIF in the inner ear. MIF-deficient mice (MIF(-/-) mice) of BALB/c background and wild-type BALB/c mice were used in this study. Expression of MIF protein in the inner ear was examined by immunohistochemistry in wild-type mice (WT). The hearing function was assessed by the click-evoked auditory brainstem response in both MIF(-/-) mice and WT at 1, 3, 6, 9, 12, and 18months of age. Morphological examination of the cochlea was also performed using scanning electron microscopy and light microscopy. MIF was observed in the spiral ligament, stria vascularis, Reissner's membrane, spiral ganglion cells (SGCs), saccular macula, and membranous labyrinth. The MIF(-/-) mice had a significant hearing loss as compared with the WT at 9, 12, and 18months of age. In the MIF(-/-) mice, scanning electron microscopy showed that the outer cochlear hair cells were affected, but that the inner cochlear hair cells were relatively well preserved. The number of SGCs was lower in the MIF(-/-) mice. MIF was strongly expressed in the mouse inner ear. Older MIF(-/-) mice showed accelerated age-related hearing loss and morphological inner ear abnormalities. These findings suggest that MIF plays an important role in the inner ear of mice.
Insights
Macrophage migration inhibitory factor (MIF) plays a crucial role in maintaining hearing function. MIF deficiency in mice accelerates age-related hearing loss and causes inner ear abnormalities.
Area of Science:
- Otolaryngology
- Immunology
- Aging Research
Background:
- Age-related hearing loss is a prevalent sensory disorder in the elderly.
- Macrophage migration inhibitory factor (MIF) is a versatile molecule with diverse biological functions.
- The specific role of MIF in the inner ear remains largely unexplored.
Purpose of the Study:
- To investigate the role of Macrophage migration inhibitory factor (MIF) in the inner ear.
- To determine the impact of MIF deficiency on age-related hearing function and cochlear morphology in mice.
Main Methods:
- Utilized Macrophage migration inhibitory factor (MIF)-deficient (MIF(-/-)) and wild-type (WT) BALB/c mice.
- Assessed hearing function using click-evoked auditory brainstem response at multiple ages (1-18 months).
- Examined inner ear morphology via immunohistochemistry, scanning electron microscopy, and light microscopy.
Main Results:
- Macrophage migration inhibitory factor (MIF) was detected in various inner ear structures, including the spiral ligament, stria vascularis, and spiral ganglion cells (SGCs).
- MIF(-/-) mice exhibited significant hearing loss compared to WT mice by 9, 12, and 18 months of age.
- Morphological analysis revealed damage to outer cochlear hair cells and reduced SGCs in MIF(-/-) mice, indicating accelerated age-related changes.
Conclusions:
- Macrophage migration inhibitory factor (MIF) is expressed in the mouse inner ear.
- MIF deficiency leads to accelerated age-related hearing loss and inner ear structural abnormalities.
- These findings highlight a significant role for MIF in maintaining inner ear integrity and auditory function.

