Hearing loss is often associated with human immune disorders, including both autoimmune disease and systemic immune complex disease. At present we have very little understanding of the cellular and molecular mechanisms of the ear that are compromised to lead to this deficit. The general aim of the study is to evaluate inner ear morphology, electrophysiology, and immunopathology in mouse models of autoimmune disease and systemic immune complex disease. C3H control mice, C3H/lpr autoimmune disease mice, and C3H mice with induced systemic immune complex disease will be evaluated with auditory brainstem response electrophysiology at ages of 2, 4, and 6 months which are before, during and after onset of autoimmune disease at 3 months. Serum analyse of antinuclear antibody, immune complexes, cryoglobulins, and total globulins will be used to assess systemic disease. Light and electron microscopy of the cochlea will indicate the areas of pathology and light and electron microscopic immunocytochemistry of immunoglobulins and complement will indicate the areas of immunopathology. Corticosteroid therapy will be attempted to prevent the effects of systemic autoimmune disease on the cochlea to identify possible interventional methods. Cochlear electrophysiology, pathology, and immunopathology will be compared in the groups to determine the extent and similarities of cochlear damage with the two immune disease models. The study will allow us to identify the potential inner ear disease mechanisms in human immune disorders. By understanding the sensorineural pathology related to these diseases, we can more effectively intervene in such cases of human inner ear dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001052-02
Application #
3217757
Study Section
Hearing Research Study Section (HAR)
Project Start
1992-09-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
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Trune, D R (1997) Cochlear immunoglobulin in the C3H/lpr mouse model for autoimmune hearing loss. Otolaryngol Head Neck Surg 117:504-8
Trune, D R; Kempton, J B; Hefeneider, S H et al. (1997) Inner ear DNA receptors in MRL/lpr autoimmune mice: potential 30 and 70 kDa link between autoimmune disease and hearing loss. Hear Res 105:57-64
Mitchell, C R; Kempton, J B; Scott-Tyler, B et al. (1997) Otitis media incidence and impact on the auditory brain stem response in lipopolysaccharide-nonresponsive C3H/HeJ mice. Otolaryngol Head Neck Surg 117:459-64
Trune, D R; Kempton, J B; Mitchell, C (1996) Decreased auditory function in the C3H/lpr autoimmune disease mouse. Hear Res 95:57-62
Mitchell, C; Kempton, J B; Creedon, T et al. (1996) Rapid acquisition of auditory brainstem responses with multiple frequency and intensity tone-bursts. Hear Res 99:38-46
Trune, D R; Kempton, J B; Mitchell, C (1996) Auditory function in the C3H/HeJ and C3H/HeSnJ mouse strains. Hear Res 96:41-5
Trune, D R; Berg, D M; DeGagne, J M (1995) Computerized digital photography in auditory research: a comparison of publication-quality digital printers with traditional darkroom methods. Hear Res 86:163-70