September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Pressure-independent outflow in ex vivo mouse eyes
Author Affiliations & Notes
  • Michael Madekurozwa
    Bioengineering, Imperial College London, London, United Kingdom
  • Joseph Michael Sherwood
    Bioengineering, Imperial College London, London, United Kingdom
  • Ester Reina-Torres
    Bioengineering, Imperial College London, London, United Kingdom
  • Jacques Alexander Bertrand
    Bioengineering, Imperial College London, London, United Kingdom
  • Darryl R Overby
    Bioengineering, Imperial College London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Michael Madekurozwa, None; Joseph Sherwood, None; Ester Reina-Torres, None; Jacques Bertrand, None; Darryl Overby, None
  • Footnotes
    Support  We thank the donors of National Glaucoma Research, a program of the BrightFocus foundation
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6424. doi:
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      Michael Madekurozwa, Joseph Michael Sherwood, Ester Reina-Torres, Jacques Alexander Bertrand, Darryl R Overby; Pressure-independent outflow in ex vivo mouse eyes. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6424.

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

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Purpose : Mice are commonly used for studies of aqueous humor dynamics, but it has been reported that up to 80% of outflow is pressure-independent, which would typically be attributed to non-trabecular routes. Such high non-trabecular outflow would invalidate the mouse as a model for human outflow, which is primarily trabecular. This study aims to directly measure pressure-independent outflow at zero pressure, Q0, in ex vivo mouse eyes. As the flow-pressure relationship is often assumed to be linear, we also examined whether non-linear behaviour could contribute to the appearance of pressure-independent outflow.

Methods : 8 pairs of enucleated eyes from C57BL/6 mice aged 9-16 weeks were perfused with PBS+5.5mM glucose using the iPerfusion system. Pressure steps of 0, 3, 6, 9, 12, 15, and 18 mmHg were applied while measuring intraocular pressure (P) and the flow rate (Q) into the eye. The contralateral eye received the same pressure regimen with an artificial pressure-independent inflow of 120 nl/min infused with a syringe pump. This was chosen to mimic reported in vivo rates of aqueous production minus pressure-independent outflow. To examine the non-linearity of the Q-P relationship, 66 additional unpaired eyes were perfused at 4-20 mmHg. Q-P data were fit by linear (Q = C P + Q0) and non-linear (Q =Cr (P / Pr)β P + Q0) models where C is the facility and Cr the facility at Pr = 8 mmHg. β is an index of non-linearity.

Results : Non-zero values of β (0.75 ± 0.63; mean ± 2SD, n=66) confirmed that the Q-P relationship was non-linear. For the artificial inflow cases, Q0 was not significantly different from zero when accounting for the resolution of the flow meter (-6 ± 2 nl/min, n=8), and Q0 was not significantly different from 120 nl/min with infusion (-115 ± 8 nl/min, n=8). There was a strong correlation between the non-linearity parameter β and Q0 predicted by the linear model (p<10-6, n=66), suggesting that non-linearity in the Q-P relationship introduces an artificial pressure-independent outflow.

Conclusions : There is negligible pressure-independent outflow in enucleated eyes from young C57BL/6 mice. Non-linearity in the Q-P relationship contributes to the artificial appearance of pressure-independent outflow when analysed using a linear model. The form of the Q-P relationship thus influences interpretation of the mechanism and pathway of outflow, and assumptions regarding linearity or constancy of outflow facility should be more carefully evaluated.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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