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Immunohistochemical localization of megalin and cubilin in the human inner ear
Seiji Hosokawa1, Kumiko Hosokawa1, Gail Ishiyama2
1Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, United States; Department of Otorhinolaryngology/Head & Neck Surgery, Hamamatsu University School of Medicine, Japan.
Abstract:
Megalin and cubilin are endocytic receptors expressed in many absorptive polarized epithelia. These receptors have been implicated in the transport of gentamicin in the inner ear as possible contributors to ototoxic damage. Megalin and cubilin have been characterized in detail in the mouse and rat inner ear, but not in the human inner ear. In this study, megalin and cubilin were localized by immunohistochemistry using affinity-purified antibodies in formalin fixed frozen cryostat and celloidin embedded sections of the human inner ear. In the cochlea megalin and cubilin were localized in marginal cells of the stria vascularis, epithelial cells of the spiral prominence and the Reissner's membrane. In the macula utricle and cristae ampullaris, megalin and cubilin were localized in transitional and dark cells, but not in vestibular hair cells and supporting cells. In the endolymphatic duct megalin and cubilin were localized in the epithelial cells. The localization of megalin and cubilin in the human inner ear is consistent with previous reports in the inner ear of animal models and suggest that these receptors may play an important role in the inner ear endocytic transport, and maybe potential targets for prevention of ototoxic damage or the delivery of medications.
Insights
Megalin and cubilin receptors were found in the human inner ear, suggesting their role in drug transport and potential ototoxic damage. This research maps their location, aiding future therapeutic strategies.
Area of Science:
- Inner ear biology
- Cellular biology
- Ototoxicology
Background:
- Megalin and cubilin are endocytic receptors involved in epithelial transport.
- These receptors are implicated in gentamicin transport and potential inner ear damage.
- Previous characterization was limited to animal models, not the human inner ear.
Purpose of the Study:
- To localize megalin and cubilin in the human inner ear.
- To investigate the role of these receptors in the human inner ear.
- To assess their potential involvement in ototoxic damage and drug delivery.
Main Methods:
- Immunohistochemistry using affinity-purified antibodies.
- Analysis of formalin-fixed frozen cryostat and celloidin-embedded human inner ear sections.
- Localization in cochlea, macula utricle, cristae ampullaris, and endolymphatic duct.
Main Results:
- Megalin and cubilin were localized in specific cells of the human cochlea, including stria vascularis and Reissner's membrane.
- In vestibular organs, these receptors were found in transitional and dark cells, but not hair or supporting cells.
- Localization was also observed in the epithelial cells of the endolymphatic duct.
Conclusions:
- The human inner ear distribution of megalin and cubilin aligns with findings in animal models.
- These receptors likely play a significant role in endocytic transport within the human inner ear.
- Megalin and cubilin represent potential targets for preventing ototoxicity and for targeted medication delivery.
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