LAB SPOTLIGHT

Human Ear Research Laboratory – Barany Laboratory 

Department of Otolaryngology – Head and Neck Surgery

Uppsala University Hospital, Sweden

Scanning electron microscopy of a human organ of hearing. The human sensory hair cells are seen (blue; outer hair cells and red; inner hair cells). These cells are surrounded by many different supporting cells. The human cochlea contains 15 000 hair cells. Only the inner hair cells (3400, red) transmit nerve signals to the brain. The outer hair cells (12000) exhibit the protein prestin (red labeling). It is expressed immunohistochemically in the cell membrane (A,B,C) and can be visualized with laser confocal microscopy. The cell cytoplasm is visualized through a marker targeting parvalbumin.

Nobel Prize winner Robert Barany was our first Professor at the Department of oto-rhino-laryngology at Uppsala University (1926-1936). He received the prize in 1914 for his discoveries of the caloric response but due to the First World War he collected it in Stockholm 1915 and chose thereafter to stay in Sweden and Uppsala. He was an ingenious scientist who combined clinical observation with physiological thinking. His science laid the ground for future vestibular research in Uppsala that included personalities like Olof Nylen, Arne Sjöberg and Jan Stahle. Olof Nylen designed the first microscope for use in ear surgery. It was under Professor Hans Engström (1968-1979) that Uppsala Clinic started to perform cellular inner ear research and he was an electron microscopist with world reputation. He created the inner ear laboratory and came from Karolinska Institute where he had worked under the famous anatomist *Fritiof Sjöstrand; a pioneer in electron microscopy. During its golden age (1951-1955) he developed a technique to cut thin sections using razor blades (Schick!) that were polished with a particular diamond powder using a glass plate inspected with epimicroscopy.Hans Engström was the first in the field of inner ear electron microscopy and was joined by Jan Wersäll; later chairman at the Dept. of ORL at Karolinska Hospital in Stockholm. Hans Engström brought his daughter Berit Engström into the field (today medical doctor in Audiology); an excellent electron microscopist. Their beautiful studies of the organ of Corti are still classic.   

Inner ear research continued under Jan Stahle´s chairmanship. He devoted his clinical career to problems around Meniere´s disease. Under his and Herrman Wilbrand´s (Professor in Oto-radiology) guidance the idea was developed to create a collection of human inner ear molds and dissections. The initiative was to delineate the miniscule structures of the human inner ear such as the vestibular and cochlear aqueducts and to observe their role in Meniere´s disease. These small canals were also associated with accessory canals housing blood vessels that were believed to play important roles for the turnover of inner ear fluid. Herrman Wilbrand had a deep interest in temporal bone anatomy and its radiological appearance and used poly-tomography before the era of modern CT. Our collaboration resulted in radio-anatomic correlations and new techniques to cast human inner ears using methacrylate and silicon with low shrinkage factor. A collection was built with 325 corrosion casts performed by several collaborators at the Dept. of Radiology. These casts are now at the Medical-History Museum and Dept. of ORL and used for research and teaching. Little did we then understand the remarkable evolution of ORL with CI and ABI and other bionic systems that we now perceive? Our collection can be used to understand the individual biological variations important for inner ear surgeons. 

Today our research department focuses on cell culture and structural analyses and proteomics of the human ear. We try to reach new information about the human ear. Today much relies on animal data. Fresh human tissue can be obtained at surgery but its scarcity limits the investigations. Recent studies reveal (and perhaps a bit surprising) differences in molecular expression. It motivates some caution in generally extrapolating animal data to man. This seems particularly relevant for the auditory nerve system. 

*Afzelius Björn. Sjöstrand F. S. (2001) Memoires, The development of Scandinavian electron microscopy. J. Submicr. Cytol. Pathol. 33 : 363-417.

By Helge Rask-Andersen MD, PhD.

Publications from Uppsala Human Ear Research Laboratory

Dept ORL, Uppsala University Hospital, Uppsala, Sweden 

  1. Barany R. Untersuchungen iiber den vom Vestibularapparat des Ohres reflektorisch ausgelosten rhytmischen Nystagmus und seine Begleiterscheinungen. Monatsschr Ohrenheilkd 1906; 40:193-297.

  2. Barany R. Nobel-Vortrag. Nord Tidskr Oto-rhino-laryngol 1916; 74: 157-74.

  3. Stahle J. Electronystagmography in the caloric test. Acta SOC Med Upsal 1956; 61: 307-32.

  4. Stahle J. Robert Baramy-ingenious scientist and farseeing physician. In: Graham MD, Kemink JL, eds. The vestibular system. Neurophysiologic and clinical research. New York: Raven Press, 1987: 17-25.

  5. Carl-Olof Nylen. The Otomicroscope and Microsurgery 1921-1971. Acat Otolaryngol 73: 453-454, 1972.

  6. Nylen CO. An oto-microscope. Acta Otolaryngol. 1923; 5:414-417.

  7. Nylen CO. The new oto-laryngological department of the University Hospital, Uppsala, Sweden. Acta Otolaryngol 1950; Suppl 87:1-16.

  8. Stahle J. Endolymphatic hydrops-fifttieth anniversary. Acta Otolaryngol 1989;468_11-16.

  9. Angelborg C, Hultcrantz E, Ågerup B: The cochlear blood flow. Acta Otolaryngol 83:92-97,1977.

  10. Rask-Andersen H, Stahle J. Immunodefence of the inner ear? Lymphocyte-macrophage interaction in the endolymphatic sac.Acta Otolaryngol Acta Otolaryngol.1980 Mar-Apr;89(3-4):283-94.

  11. Engström, H, Ades HW, Hawkins JE, Jr. Structure and Functions of the Sensory Hairs of the Inner Ear J. Acoust. Soc. Am. Volume 34, Issue 9B, pp. 1356-1363 (September 1962).

  12. Rask-Andersen H, Boström M, Gerdin B, Kinnefors A, Nyberg G, Engstrand T, Miller J M & Lindholm D. Regeneration of human auditory nerve. In vitro/ in video Demonstration of Neural Progenitor Cells in Adult Human and Guinea Pig Spiral Ganglion. Hear Res. 2005 May; 203(1-2):180-91.

  13. Hirt B, Penkova ZH, Eckard A, Liu W, Rask-Andersen H, Müller, Löwenheim H. The subcellular distribution of aquaporin 5 in the cochlea reveals a water shunt at the perilymph-endolymph barrier. Neuroscience 168 (2010) 957–970.

  14. Boström M, Khalifa S, Boström M, Liu, W, Friberg U, Rask-Andersen H. Effects of Neurotrophic Factors on Growth and Glia Cell Alignment of Cultured Adult Spiral Ganglion Cells. Audiol Neurotol 2010;15:175–186.

  15. Liu W, Boström M, Kinnefors A, Rask-Andersen H. Unique expression of connexins in the human cochlea. Hearing Research 250 (2009) 55–62.

  16. Rask-Andersen H,Liu W, Bostrom M, Pfaller K, Kinnefors A, Glueckert R, Schrott-Fischer A.Immunolocalization of Prestin in the Human Cochlea. Audiol Med 2009.

  17. Stjernschantz J, Wentzel P, Rask-Andersen H. Localization of prostanoid receptors and cyclo-oxygenase enzymes in guinea pig and human cochlea. Hear Res. 2004 Nov; 197(1-2):65-73.

  18. Knutsson J, von Unge M, Rask-Andersen H. Localization of Progenitor/Stem Cells in the Human Tympanic Membrane.Audiol Neurootol. 2010 Nov 4;16(4):263-269.

  19. H. Rask-Andersen, A. Kinnefors, R.-B. Illing. On a novel type of neuron with proposed mechanoreceptor function in the human round window membrane. An immunohistochemical study, Revue Portman (1999) Rev Laryngol Otol Rhinol (Bord)120 (1999), pp. 203–207.

Address for correspondence:

Rask-Andersen, Helge. M.D, Ph.D.
Department of Otolaryngology – Head and Neck Surgery
Dept of ORL, Uppsala University Hospital
751 85 Uppsala
Sweden

E-mail: helge.rask-andersen@akademiska.se