Two specific aims were delineated: First, morphological, immunohistochemical, and molecular genetic evidence suggest that measles virus is present in otosclerotic lesions. Paramyxoviruses have been implicated in other osseous dysplasias (e.g. Paget's disease). The investigators plan to search for measles virus RNA in otosclerotic temporal bones. The applicant wi draw upon the extensive archival collection at the Massachusetts Eye and Ear Infirmary (MEEI) which includes 205 sets of otosclerotic temporal bones. Recently, the osteogenesis imperfecta (OI) associated gene COL 1A1 has been implicated in otosclerosis. The hypothesis is that otosclerosis represents a minor variant of OI and possesses a similar dysfunction in type 1 collagen. They have in hand samples from 220 individuals from 65 families with otosclerosis. The second line of investigation involves mtDNA mutations associated with presbycusis. The MEEI archival temporal bone collection contains 142 sets of temporal bones with various types of presbycusis (28 sensory, 70 neural, 44 strial). Comprehensive audiological profiles are available. Sensorineural hearing loss is present in virtually all known varieties of mitochondrial dysfunction. Mitochondrial mutations appear to accumulate with advancing age. The investigators plan to search for a variety of point mutations as well as sequential deletions in mtDNA obtained from their archival collection. Collection of audiological data from patients with known mitochondrial mutatio will also be undertaken.
| Stankovic, Konstantina M; Adachi, Osamu; Tsuji, Kunikazu et al. (2010) Differences in gene expression between the otic capsule and other bones. Hear Res 265:83-9 |
| Stankovic, Konstantina M; Kristiansen, Arthur G; Bizaki, Argyro et al. (2007) Studies of otic capsule morphology and gene expression in the Mov13 mouse--an animal model of type I osteogenesis imperfecta. Audiol Neurootol 12:334-43 |
| McKenna, Michael J; Kristiansen, Arthur G (2007) Molecular biology of otosclerosis. Adv Otorhinolaryngol 65:68-74 |
| Chen, Zhiqiang; Mikulec, Anthony A; McKenna, Michael J et al. (2006) A method for intracochlear drug delivery in the mouse. J Neurosci Methods 150:67-73 |
| Stankovic, Konstantina M; McKenna, Michael J (2006) Current research in otosclerosis. Curr Opin Otolaryngol Head Neck Surg 14:347-51 |
| Zehnder, Andreas F; Kristiansen, Arthur G; Adams, Joe C et al. (2005) Osteoprotegerin in the inner ear may inhibit bone remodeling in the otic capsule. Laryngoscope 115:172-7 |
| Chen, Zhiqiang; Kujawa, Sharon G; McKenna, Michael J et al. (2005) Inner ear drug delivery via a reciprocating perfusion system in the guinea pig. J Control Release 110:1-19 |
| McKenna, Michael J; Nguyen-Huynh, Anh T; Kristiansen, Arthur G (2004) Association of otosclerosis with Sp1 binding site polymorphism in COL1A1 gene: evidence for a shared genetic etiology with osteoporosis. Otol Neurotol 25:447-50 |
| Clayton, Amy E; Mikulec, Anthony A; Mikulec, Katharine H et al. (2004) Association between osteoporosis and otosclerosis in women. J Laryngol Otol 118:617-21 |
| Johns, Donald R; Colby, Kathryn A (2002) Treatment of Leber's hereditary optic neuropathy: theory to practice. Semin Ophthalmol 17:33-8 |
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