In the present proposal we will preserve, process and make available human ear tissue specimens for inner ear basic science researchers such that they may be able to compare with their animal models. The use of celloidin and microdissected human temporal bone tissue for immunohistochemical and quantitative techniques will be instrumental in driving basic animal inner ear research forward towards understanding of human ear pathology and has high potential for the development of effective drug therapies for restoring auditory and vestibular function.
In Specific Aim 1) we will improve access for the auditory and vestibular research community to human ear tissues from temporal bone specimens. We will improve and promote timely procurement, preparing and processing of new specimens, and appropriate re-processing of archived specimens. We will distribute a limited number of well-prepared laboratory tissues to funded researchers who lack adequate access to facilities for human temporal bone preparation. We will also exploit use of the Registry for information about currently archived tissues and their access by the community, and promote collaborations between researchers seeking to validate animal models for human relevance.
Specific Aim 2) We will optimize tissue preparation techniques. We will include molecular and cellular marking and visualization techniques that allow direct comparisons of fresh and archived human tissues with those from animal models. We will disseminate protocols for procurement, preservation and preparation of human ear tissues from temporal bones. By doing this we will encourage animal researchers to include human tissues into their analyses.
Specific Aim 3) We will use high resolution MRI to evaluate the fluid-filled inner ear structures, and ex vivo MRI to evaluate the inner ear structures post-mortem and make comparisons with celloidin- embedded histopathology. We will exploit new technologies and methods to image and visualize human middle and inner ears in situ with the aim of visualizing soft cellular tissues, membranes and fluids, as well as hard bony tissues.
Specific Aim 4) We will provide technical instruction with hands-on training will be available for investigators, technicians otolaryngology residents, medical school and graduate students interested in inner ear biology in the temporal bone processing techniques and skills needed for processing human ear tissues from temporal bones. The materials generate in this proposal will be mutually beneficial for researchers in basic scientific studies of the inner ear, as well as to temporal bone scientists wishing to apply high levels of molecular and cellular techniques to the human temporal bone. These collaborative efforts hold promise to rapidly accelerate the science of temporal bone processing and the understanding of human otopathologies.
To advance in the temporal bone sciences we will promote and share human ear tissue with basic inner ear researchers. We will provide instruction to the scientific community to handled, acquire, stain and process human ear tissue. We will further to develop better techniques to identify cellular component in the human inner ear using immunofluorescence and transmission electron microscopy.
|Hosokawa, Seiji; Hosokawa, Kumiko; Ishiyama, Gail et al. (2018) Immunohistochemical localization of megalin and cubilin in the human inner ear. Brain Res 1701:153-160|
|Hosokawa, Kumiko; Hosokawa, Seiji; Ishiyama, Gail et al. (2018) Immunohistochemical localization of Nrf2 in the human cochlea. Brain Res 1700:1-8|
|Ishiyama, Gail; Wester, Jacob; Lopez, Ivan A et al. (2018) Oxidative Stress in the Blood Labyrinthine Barrier in the Macula Utricle of Meniere's Disease Patients. Front Physiol 9:1068|
|Linthicum Jr, Fred H; Doherty, Joni K; Lopez, Ivan A et al. (2017) Cochlear implant histopathology. World J Otorhinolaryngol Head Neck Surg 3:211-213|