Why Study Human Temporal Bones?

Human temporal bones provide an irreplaceable and invaluable resource for the study of the pathology and pathophysiology of disorders of hearing, balance and facial nerve function.  There are many reasons why it is critical to continue to study human temporal bones that have been acquired at autopsy:

        1. The molecular bases of auditory and vestibular disorders are being uncovered at a very rapid pace.  Paradoxically, very little is known about the underlying temporal bone histopathology in genetic deafness.  To date, more than 150 loci have been identified for various syndromic and non-syndromic hearing impairments, and the responsible genes have been cloned in more than 60 conditions (hereditary hearing loss homepage, http://webh01.ua.ac.be/hhh/).  On a worldwide basis, there have been less than 15 case reports of otopathology in patients with genetic deafness where the precise genetic mutation was known.  Given the variant clinical expressions of syndromes of genetic deafness, it becomes urgent to provide pathologic profiles that can be matched to the genetic abnormalities.  Without this knowledge, it will be difficult to ultimately devise strategies for overcoming the genetic defects.  Animal models, both knockouts, knockins and naturally occurring mutants, are being increasingly used to investigate the genetics of hearing loss.  Such models can provide valuable information regarding the molecular bases of auditory and vestibular disorders, but it will be important to verify the validity of these models by comparison with the otopathology as determined in human cases.  Studying human specimens can generate hypotheses regarding pathways and mechanisms of hearing loss, which can then be tested experimentally in a suitable animal model.  Thus, human and animal otopathology are complementary in terms of the information they can provide to researchers interested in genetics of hearing impairment.  There are also many syndromes of hearing loss for which no animal models currently exist, and so the study of human specimens in such cases becomes important.

        2. We now have molecular and cellular histopathologic tools that can be used to investigate the pathophysiological bases for specific temporal bone and brain disorders.  In addition to traditional light and electron microscopy, techniques such as polymerase chain reaction (PCR) amplification of DNA and mRNA, in-situ hybridization, immunostaining and emerging technologies for proteomics research can now be applied to temporal bone and brain specimens which holds great promise in improving knowledge of the molecular pathology of hearing and balance disorders. 

        3. In addition to genetic disorders, there are many other conditions for which there are no or few human temporal bone specimens.  Examples include Bell's palsy, sudden idiopathic deafness, vestibular neuritis, perilymphatic leak, etc.  Unless we understand the pathologic bases for these disorders, it is difficult to implement rational diagnostic and therapeutic modalities.  Also, there are still a number of common otologic disorders such as chronic otitis media and otosclerosis for which there are no counterparts in animals, and hence, many questions concerning pathology and pathophysiology cannot be answered in the experimental animal.

        4. Another important area for study is to evaluate the efficacy of otologic surgery on the ear.  For example, there are very few well-documented specimens from patients who have undergone surgery for Meniere's disease.  Hundreds of operations are performed annually for Meniere's disease and we do not know whether these procedures actually do what they are supposed to.  Over 50,000 cochlear implants have been inserted, and yet, less than 50 temporal bones with implants are available nationwide.  Elucidation of the histopathologic changes after otologic surgery can lead to a better understanding of the success or otherwise of these procedures and also lead to improvements in techniques and technologies.

        5. Finally, there are very few temporal bone specimens that have been procured from normal individuals with well documented normal levels of hearing and balance function.  Normal specimens are essential to serve as controls, especially in studies utilizing molecular and cellular methods of investigation.  For example, in order to investigate whether mitochondrial mutations result in presbycusis, one needs temporal bone sections from well-defined normal controls.

Mass Eye and Ear Infimary Harvard NIDCD