Imperial College London
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ProfessorDarrylOverby

Faculty of Engineering, Department of Bioengineering

Professor of Mechanobiology
 
 
 
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Contact

 

+44 (0)20 7594 6376d.overby

 
 
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Location

 

3.07Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{McDonnell:2020:10.1038/s41598-020-62730-4,
author = {McDonnell, F and Perkumas, KM and Ashpole, NE and Kalnitsky, J and Sherwood, JM and Overby, DR and Stamer, WD},
doi = {10.1038/s41598-020-62730-4},
journal = {Scientific Reports},
title = {Shear stress in Schlemm's canal as a sensor of intraocular pressure},
url = {http://dx.doi.org/10.1038/s41598-020-62730-4},
volume = {10},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Elevated intraocular pressure (IOP) narrows Schlemm's canal (SC), theoretically increasing luminal shear stress. Using engineered adenoviruses containing a functional fragment of the shear-responsive endothelial nitric oxide synthase (eNOS) promoter, we tested effects of shear stress and elevated flow rate on reporter expression in vitro and ex vivo. Cultured human umbilical vein endothelial cells (HUVECs) and SC cells were transduced with adenovirus containing eNOS promoter driving secreted alkaline phosphatase (SEAP) or green fluorescent protein (GFP) and subjected to shear stress. In parallel, human anterior segments were perfused under controlled flow. After delivering adenoviruses to the SC lumen by retroperfusion, the flow rate in one anterior segment of pair was increased to double pressure. In response to high shear stress, HUVECs and SC cells expressed more SEAP and GFP than control. Similarly, human anterior segments perfused at higher flow rates released significantly more nitrites and SEAP into perfusion effluent, and SC cells expressed increased GFP near collector channel ostia compared to control. These data establish that engineered adenoviruses have the capacity to quantify and localize shear stress experienced by endothelial cells. This is the first in situ demonstration of shear-mediated SC mechanobiology as a key IOP-sensing mechanism necessary for IOP homeostasis.
AU  - McDonnell,F
AU  - Perkumas,KM
AU  - Ashpole,NE
AU  - Kalnitsky,J
AU  - Sherwood,JM
AU  - Overby,DR
AU  - Stamer,WD
DO  - 10.1038/s41598-020-62730-4
PY  - 2020///
SN  - 2045-2322
TI  - Shear stress in Schlemm's canal as a sensor of intraocular pressure
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-020-62730-4
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32242066
UR  - http://hdl.handle.net/10044/1/78844
VL  - 10
ER  -
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