Outer Hair Cell Electromotility in vivo

2011 ◽  
Author(s):  
Sripriya Ramamoorthy ◽  
Alfred L. Nuttall ◽  
Christopher A. Shera ◽  
Elizabeth S. Olson
Keyword(s):  
PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e32757 ◽  
Author(s):  
Dingjun Zha ◽  
Fangyi Chen ◽  
Sripriya Ramamoorthy ◽  
Anders Fridberger ◽  
Niloy Choudhury ◽  
...  

2012 ◽  
Vol 102 (3) ◽  
pp. 388-398 ◽  
Author(s):  
Sripriya Ramamoorthy ◽  
Alfred L. Nuttall

2020 ◽  
Author(s):  
Ghazal Babolmorad ◽  
Asna Latif ◽  
Niall M. Pollock ◽  
Ivan K. Domingo ◽  
Cole Delyea ◽  
...  

AbstractToll-like receptor 4 (TLR4) is famous for recognizing the bacterial endotoxin lipopolysaccharide (LPS) as its canonical ligand. TLR4 is also activated by other classes of agonist including some Group 9/10 transition metals. Roles for these non-canonical ligands in pathobiology mostly remain obscure, though TLR4 interactions with metals can mediate immune hypersensitivity reactions. In this work, we tested whether TLR4 can be activated by the Group 10 transition metal, platinum. We demonstrated that in the presence of TLR4, platinum activates pathways downstream of TLR4 to a similar extent as the known TLR4 agonists LPS and nickel. Platinum is the active moiety in cisplatin, a very potent and invaluable chemotherapeutic used to treat solid tumors in childhood cancer patients. Unfortunately, cisplatin use is limited due to an adverse effect of permanent hearing loss (cisplatin-induced ototoxicity, CIO). Herein, we demonstrated that cisplatin also activates TLR4, prompting the hypothesis that TLR4 mediates aspects of CIO. Cisplatin activation of TLR4 was independent of the TLR4 co-receptors CD14 and MD-2, which is consistent with TLR4 signaling elicited by transition metals. We found that TLR4 is required for cisplatin-induced inflammatory, oxidative and apoptotic responses in an ear outer hair cell line and for hair cell damage in vivo. Thus, TLR4 is a promising therapeutic target to mitigate CIO. We additionally identify a TLR4 small molecule inhibitor able to curtail cisplatin toxicity in vitro. Further work is warranted towards inhibiting TLR4 as a route to mitigating this adverse outcome of childhood cancer treatment.Significance StatementThis work identifies platinum, and its derivative cisplatin, as new agonists for TLR4. TLR4 contributes to cisplatin-induced hair cell death in vitro and in vivo. Genetic and small molecule inhibition of TLR4 identify this receptor as a druggable therapeutic target with promise to curtail cisplatin-induced ototoxicity, a devastating side-effect of an otherwise invaluable chemotherapeutic tool.


1997 ◽  
Vol 112 (1-2) ◽  
pp. 134-140 ◽  
Author(s):  
Ye Liu ◽  
Deepa Rao ◽  
Laurence D. Fechter

2021 ◽  
Author(s):  
Nam Hyun Cho ◽  
Haobing Wang ◽  
Sunil Puria

Because it is difficult to directly observe the morphology of the living cochlea, our ability to infer the mechanical functioning of the living ear has been limited. Nearly all of our knowledge about cochlear morphology comes from postmortem tissue that was fixed and processed using procedures that possibly distort the structures and fluid spaces of the organ of Corti. In this study, optical coherence tomography was employed to obtain in vivo and postmortem micron-scale volumetric images of the high-frequency hook region of the gerbil cochlea through the round-window membrane. The anatomical structures and fluid spaces of the organ of Corti were segmented and quantified in vivo and over a 90-minute postmortem period. The results show that some aspects of the organ of Corti are significantly altered over the course of death, such as the volumes of the fluid spaces, whereas the dimensions of other features change very little. We postulate that the fluid space of the outer tunnel and its surrounding tectal cells form a resonant structure that can affect the motion of the reticular lamina and thereby have a profound effect on outer-hair-cell transduction and thus cochlear amplification. In addition, the in vivo fluid pressure of the inner spiral sulcus is postulated to effectively inflate the connected sub-tectorial gap between the tectorial membrane and the reticular lamina. This gap height decreases after death, which is hypothesized to reduce and disrupt hair-cell transduction.


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