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The Journal of Neuroscience, March 15, 1999, 19(6):2161-2170

Immunocytochemical and Morphological Evidence for Intracellular Self-Repair as an Important Contributor to Mammalian Hair Cell Recovery

J. Lisa Zheng1, Gilbert Keller2, and Wei-Qiang Gao1

Departments of 1 Neuroscience and 2 Pharmacokinetics and Metabolism, Genentech, South San Francisco, California 94080

Although recent studies have provided evidence for hair cell regeneration in mammalian inner ears, the mechanism underlying this regenerative process is still under debate. Here we report immunocytochemical, histological, electron microscopic, and autoradiographic evidence that, in cultured postnatal rat utricles, a substantial number of hair cells can survive gentamicin insult even their stereocilia are lost. These partially damaged hair cells can survive for a prolonged time and regrow the stereocilia. Although the number of stereocilia-bearing hair cells increases over time after gentamicin insult, hair cell and supporting cell numbers remain essentially unchanged. Tritiated thymidine autoradiography and bromodeoxyuridine immunocytochemistry of the cultures demonstrate that cell proliferation in the sensory epithelium is very limited and is far below the number of recovered hair cells. Furthermore, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling analysis indicates that gentamicin-induced apoptosis in the sensory epithelium occurs mainly during a 2 d treatment period, and additional cell death is minimal 2-11 d after treatment. Considered together, intracellular repair of partially damaged hair cells can be an important contributor to spontaneous hair cell recovery in mammalian inner ears.

Key words: hair cells; supporting cells; regeneration; self-repair; apoptosis; proliferation; vestibular; utricle; inner ear; gentamicin; autoradiography

Copyright © 1999 Society for Neuroscience  0270-6474/99/1962161-10$05.00/0


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