June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Factors affecting oscillatory shear stress in Schlemm's canal
Author Affiliations & Notes
  • Joseph Michael Sherwood
    Bioengineering, Imperial College London, London, United Kingdom
  • W Daniel Stamer
    Opthalmology, Duke University, Durham, North Carolina, United States
  • Darryl R Overby
    Bioengineering, Imperial College London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Joseph Sherwood, None; W Daniel Stamer, None; Darryl Overby, None
  • Footnotes
    Support  NIH Grant EY022359
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2454. doi:
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      Joseph Michael Sherwood, W Daniel Stamer, Darryl R Overby; Factors affecting oscillatory shear stress in Schlemm's canal. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2454.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Shear stress acting on Schlemm’s canal (SC) endothelium plays a key role in IOP regulation by controlling shear-induced production of nitric oxide. Shear stress within SC is oscillatory due to IOP fluctuations associated with the ocular pulse. We developed a mathematical model to investigate the factors affecting the oscillatory shear stress in SC under normal and glaucomatous conditions.

Methods : We modified the steady-state model of Johnson and Kamm [1] to account for oscillatory flow in SC. The model was coupled upstream to a lumped parameter model of the whole globe and downstream to episcleral vessels, accounting for distal resistance, ocular rigidity, and oscillatory blood flow in the intra- and episcleral blood vessels. To investigate glaucoma, we increased trabecular meshwork stiffness (E) and the resistance, rje, attributable to the juxtacanicular tissue and SC inner wall. Solution of the model used iterative estimation of IOP for a given rje, with the constraint that total outflow balanced aqueous humor production.

Results : As rje increased from 1.7 to 10 mmHg/µl/min (spanning normotensive to hypertensive conditions; IOP=14-33 mmHg), mean shear stress in SC increased from 1 to 18 dyne/cm2 (blue curve in Figure 1). The variations in peak-to-peak shear stress were nearly 2-fold larger than the mean value, increasing from 1 to 37 dyne/cm2 over the same range of rje (blue shading).

Doubling the TM stiffness reduced the mean shear stress by a factor of 10, and the peak-to-peak variations by a factor of 5 (green). Increasing TM stiffness by a factor of 4 almost eliminated the shear response (red).

Conclusions : Under normal conditions, the oscillatory shear stress within SC is extremely sensitive to outflow resistance of the inner wall/JCT. This mechanism may underlie a homeostatic response, mediated by shear-induced nitric oxide production to oppose any increase in outflow resistance that would otherwise tend to elevate IOP. Increased TM stiffness, as occurs in glaucoma, suppresses this feed-back mechanism and may exacerbate IOP dysregulation.

References: [1] Johnson and Kamm, IOVS 24:320-325, 1983.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Figure 1 - Shear stress at a collector channel ostium as a function of inner wall and JCT resistance. Solid lines show temporally averaged values and shaded regions show range. Comparison of normal TM stiffness and 2- or 4-fold increases.

Figure 1 - Shear stress at a collector channel ostium as a function of inner wall and JCT resistance. Solid lines show temporally averaged values and shaded regions show range. Comparison of normal TM stiffness and 2- or 4-fold increases.

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