Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2

Otolith organs of the inner ear are innervated by two parallel afferent projections to the brainstem and cerebellum. These innervations were proposed to segregate across the line of polarity reversal (LPR) within each otolith organ, which divides the organ into two regions of hair cells (HC) with opposite stereociliary orientation. The relationship and functional significance of these anatomical features are not known.Here, we show regional expression of Emx2 in otolith organs, which establishes LPR, mediates the neuronal segregation across LPR and constitutes the bidirectional sensitivity function. Conditional knockout (cKO) of Emx2 in HCs lacks LPR. Tmie cKO, in which mechanotransduction was abolished selectively in HCs within the Emx2 expression domain also lacks bidirectional sensitivity. Analyses of both mutants indicate that LPR is specifically required formice to swimcomfortably and to traverse a balance beam efficiently, but LPR is not required formice to stay on a rotating rod

光干渉断層計によるマウス蝸牛の生存下での観察

Final publication is available at http://journals.lww.com/otology-neurotology/Pages/default.aspx京都大学0048新制・課程博士博士(医学)甲第19574号医博第4081号新制||医||1013(附属図書館)32610京都大学大学院医学研究科医学専攻(主査)教授 渡邉 大, 教授 伊佐 正, 教授 一山 智学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Estimation of the Degree of Endolymphatic Hydrops Using Optical Coherence Tomography

This study was presented at the Symposium on Biomedical Engineering 2015, Okayama, September, 2015.Endolymphatic hydrops is a disorder in which an excessive amount of endolymph fluid causes an increase in the pressure of the endolymphatic system of the inner ear. In cochlea, endolymphatic hydrops can cause stretching in the scala media, a tubular construction that, along with two other similar structures, the scala vestibuli and scala tympani, runs through the cochlea from the base to the top. Visualizing the enlargement of the scala media has traditionally been done by histological study of tissue sections, and the degree can be calculated by comparing the ratio of the area of the scala media to the combined total area of the three compartments. However, this requires the obtainment of tissue samples, and thus is not suited for in vivo measurements, and is a labor intensive process in general. Imaging modalities that have been used to measure endolymphatic hydrops include MRI, μMRI and μCT. Recently, optical coherence tomography (OCT) has been applied for visualizing cochlea of mice in vivo. However, just visually discriminating between healthy and afflicted cochlea, and judging the degree of affliction can be difficult. Thus, we aim to establish a new technique for estimating the degree of enlargement of the scala media. We measured two healthy and two diseased cochlea using conventional area calculation, as well as our method, and present results that show that our technique correlates with established standards for measuring the degree of endolymphatic hydrops in cochlea (R=0.977, p=0.5×10⁻⁷)

Therapeutic potential of a gamma-secretase inhibitor for hearing restoration in a guinea pig model with noise-induced hearing loss.

[Background]Notch signaling plays a crucial role in the fate determination of cochlear progenitor cells, hair cells, and supporting cells in the developing cochlea. Recent studies have demonstrated the temporal activation of Notch signaling in damaged mature cochleae, and have demonstrated the induction of new hair cells by pharmacologically inhibiting Notch signaling. The present study aimed to illustrate the feasibility of pharmacologically inhibiting Notch signaling by using a gamma-secretase inhibitor for treating sensorineural hearing loss. [Results]The effect of the sustained local delivery of MDL28170, a gamma-secretase inhibitor, on hearing and hair cell induction was tested in a guinea pig model with noise-induced hearing loss. MDL28170 was directly delivered into the cochlear fluids via a micro-osmotic pump. Drug application was initiated 7 days after noise exposure. Measurements of auditory brainstem responses revealed better hearing in the MDL28170-treated animals than in the vehicle controls. Histological analysis demonstrated a higher number of outer hair cells in the MDL28170-treated cochleae than the vehicle-treated cochleae. [Conclusion]These findings strongly suggest that local sustained delivery of a gamma-secretase inhibitor into the cochlea could be a novel strategy for treating acute hearing loss that is refractory to conventional treatment

Estimation of the Degree of Endolymphatic Hydrops Using Optical Coherence Tomography

This study was presented at the Symposium on Biomedical Engineering 2015, Okayama, September, 2015.Endolymphatic hydrops is a disorder in which an excessive amount of endolymph fluid causes an increase in the pressure of the endolymphatic system of the inner ear. In cochlea, endolymphatic hydrops can cause stretching in the scala media, a tubular construction that, along with two other similar structures, the scala vestibuli and scala tympani, runs through the cochlea from the base to the top. Visualizing the enlargement of the scala media has traditionally been done by histological study of tissue sections, and the degree can be calculated by comparing the ratio of the area of the scala media to the combined total area of the three compartments. However, this requires the obtainment of tissue samples, and thus is not suited for in vivo measurements, and is a labor intensive process in general. Imaging modalities that have been used to measure endolymphatic hydrops include MRI, μMRI and μCT. Recently, optical coherence tomography (OCT) has been applied for visualizing cochlea of mice in vivo. However, just visually discriminating between healthy and afflicted cochlea, and judging the degree of affliction can be difficult. Thus, we aim to establish a new technique for estimating the degree of enlargement of the scala media. We measured two healthy and two diseased cochlea using conventional area calculation, as well as our method, and present results that show that our technique correlates with established standards for measuring the degree of endolymphatic hydrops in cochlea (R=0.977, p=0.5×10⁻⁷)