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Electron microscopy of degenerative changes in the chick basilar papilla after gentamicin exposure
Keiko Hirose1, Lesnick E Westrum, Dale E Cunningham
1Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195, USA.
Insights
Gentamicin-induced hair cell degeneration in chicks shows rapid extrusion of damaged auditory hair cells. This process preserves the reticular lamina and minimizes cellular debris, offering insights into cochlear protection.
Area of Science:
- Ototoxicity research
- Cell biology
- Auditory neuroscience
Background:
- Gentamicin is a known ototoxic antibiotic.
- Auditory hair cell degeneration is a significant cause of hearing loss.
- Understanding the cellular mechanisms of hair cell death is crucial for developing protective strategies.
Purpose of the Study:
- To investigate the sequential substructural alterations in chick basilar papilla hair cells following gentamicin exposure.
- To identify the earliest signs of hair cell degeneration and the subsequent cellular events.
- To elucidate the mechanism of hair cell loss and its impact on surrounding structures.
Main Methods:
- Sequential transmission electron microscopy of chick basilar papilla.
- Gentamicin injection (300 mg/kg) in 3-day posthatch chicks.
- Sampling at 6, 8, 12, 15, 18, 21, and 24 hours post-injection.
Main Results:
- Early structural changes in hair cells observed by 8-12 hours, including swelling and mitochondrial dilation.
- Lysosome accumulation and afferent terminal swelling noted by 15-18 hours, preceding cell extrusion.
- By 21-24 hours, supporting cells formed expanded processes, maintaining junctions and encapsulating extruded hair cells.
Conclusions:
- Auditory hair cells undergo a rapid, controlled extrusion process during degeneration.
- This extrusion mechanism preserves the reticular lamina integrity.
- The process minimizes contamination of surrounding tissues by damaged hair cell contents.
Abstract:
We present a sequential study of the substructural alterations in the chick basilar papilla at the earliest signs of hair cell degeneration. Three-day posthatch chicks received a single injection of gentamicin (300 mg/kg) and were killed at 6, 8, 12, 15, 18, 21, and 24 hours after the injection. The basilar papillae were studied by conventional transmission electron microscopy. Examination was limited to the basal region, where all hair cells are eliminated by this treatment. As early as 8 hours and clearly by 12 hours, altered fine structure was seen in hair cells. Changes included rounding and swelling of the hair cells, condensation of nuclear chromatin, dissolution of ribosomes, dilatation of the mitochondria, and accumulation of inclusion bodies and lysosomes. By 15-18 hours, lysosomes increased and became denser, afferent terminals appeared swollen, and the first cell extrusion was seen. Efferents were unaffected, and supporting cells, though having inclusion bodies now, retained normal intercellular junctions. By 21-24 hours, large regions of complete hair cell loss were composed of expanded supporting cell processes with normal-appearing intercellular junctions and portions of extruded hair cells, partially attached to the supporting cell surface. These observations demonstrate that auditory hair cells undergo a rapid and controlled process of hair cell extrusion that allows preservation of the reticular lamina and minimal contamination of surrounding structures by intracytoplasmic contents of the damaged hair cells.
