Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

Abstract

The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Humans with an autosomal dominant C1509G mutation in alpha-tectorin, a protein constituent of the TM, are born with a partial hearing loss that worsens over time. The Tecta C1509/+ transgenic mouse with the same point mutation has partial hearing loss secondary to a shortened TM that only contacts the first row of OHCs. As well, Tecta C1509G/+ mice have increased expression of the OHC electromotility protein, prestin. We sought to determine whether these changes impact OHC survival. Distortion product otoacoustic emission thresholds in a quiet environment did not change to 6 months of age. However, noise exposure produced acute threshold shifts that fully recovered in Tecta +/+ mice but only partially recovered in Tecta C1509G/+ mice. While Tecta +/+ mice lost OHCs primarily at the base and within all three rows, Tecta C1509G/+ mice lost most of their OHCs in a more apical region of the cochlea and nearly completely within the first row. In order to estimate the impact of a shorter TM on the forces faced by the stereocilia within the first OHC row, both the wild type and the heterozygous conditions were simulated in a computational model. These analyses predicted that the shear force on the stereocilia is~50% higher in the heterozygous condition. We then measured electrically induced movements of the reticular lamina in situ and found that while they decreased to the noise floor in prestin null mice, they were increased by 4.58 dB in Tecta C1509G/+ mice compared to Tecta +/+ mice. The increased movements were associated with a fourfold increase in OHC death as measured by vital dye staining. Together, these findings indicate that uncoupling the TM from some OHCs leads to partial hearing loss and places the remaining coupled OHCs at higher risk. Both the mechanics of the malformed TM and the increased prestin-related movements of the organ of Corti contribute to this higher risk profile.

Mechanisms of Hearing Loss after Blast Injury to the Ear

“…Our finding of OHC loss in mice in the cochlear base is similar to other reports describing blast-induced hearing loss in rats [37] and after noise exposure in mice [40]. The SGN loss we noted also is similar to that seen after noise exposure in mice [27], [41], [42], [43].…”

In vivo vibrometry inside the apex of the mouse cochlea using spectral domain optical coherence tomography

“…We compared the results to measurements made with a commercial laser Doppler vibrometer (LDV) (OFV-5000, Polytech, Irvine, CA) that we have used previously for in vitro cochlear experiments [21,22]. The LDV was incorporated into the sample path of the OCT system as shown in Fig.…”

Three-Dimensional Imaging of the Mouse Organ of Corti Cytoarchitecture for Mechanical Modeling

“…(2) For the in situ fixed preparations, prestin immunolabeling was performed within the intact cochlea to visualize OHCs [9]. We also performed simultaneous phalloidin labeling to label actin [5]. (3) For the in situ live preparation, the cochlea was extracted from the skull and transferred to a dish prepared with agar on the bottom, which adheres to the bony capsule and thus stabilizes it for imaging.…”