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Measurement of outflow facility using iPerfusion

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Title: Measurement of outflow facility using iPerfusion
Authors: Sherwood, JM
Reina-Torres, E
Bertrand, J
Rowe, B
Overby, DR
Item Type: Journal Article
Abstract: Elevated intraocular pressure (IOP) is the predominant risk factor for glaucoma, and reducing IOP is the only successful strategy to prevent further glaucomatous vision loss. IOP is determined by the balance between the rates of aqueous humour secretion and outflow, and a pathological reduction in the hydraulic conductance of outflow, known as outflow facility, is responsible for IOP elevation in glaucoma. Mouse models are often used to investigate the mechanisms controlling outflow facility, but the diminutive size of the mouse eye makes measurement of outflow technically challenging. In this study, we present a new approach to measure and analyse outflow facility using iPerfusion™, which incorporates an actuated pressure reservoir, thermal flow sensor, differential pressure measurement and an automated computerised interface. In enucleated eyes from C57BL/6J mice, the flow-pressure relationship is highly non-linear and is well represented by an empirical power law model that describes the pressure dependence of outflow facility. At zero pressure, the measured flow is indistinguishable from zero, confirming the absence of any significant pressure independent flow in enucleated eyes. Comparison with the commonly used 2-parameter linear outflow model reveals that inappropriate application of a linear fit to a non-linear flow-pressure relationship introduces considerable errors in the estimation of outflow facility and leads to the false impression of pressure-independent outflow. Data from a population of enucleated eyes from C57BL/6J mice show that outflow facility is best described by a lognormal distribution, with 6-fold variability between individuals, but with relatively tight correlation of facility between fellow eyes. iPerfusion represents a platform technology to accurately and robustly characterise the flow-pressure relationship in enucleated mouse eyes for the purpose of glaucoma research and with minor modifications, may be applied in vivo to mice, as well as to eyes from other species or different biofluidic systems.
Issue Date: 7-Mar-2016
Date of Acceptance: 17-Feb-2016
URI: http://hdl.handle.net/10044/1/30378
DOI: 10.1371/journal.pone.0150694
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Start Page: 1
End Page: 29
Journal / Book Title: PLoS One
Volume: 11
Issue: 3
Copyright Statement: © 2016 Sherwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
BrightFocus Foundation
National Institutes of Health
Fight For Sight
National Institutes of Health
Funder's Grant Number: EP/J010499/1
G2013048
203-1774
Ref: 1385
SP0028943-PROJ0007600
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
AQUEOUS-HUMOR DYNAMICS
INTRAOCULAR-PRESSURE
GLAUCOMA PROGRESSION
TRABECULAR MESHWORK
VENOUS-PRESSURE
MOUSE
PERFUSION
MICE
ANESTHESIA
RESISTANCE
Animals
Glaucoma
Intraocular Pressure
Linear Models
Male
Mice
Mice, Inbred C57BL
Perfusion
Animals
Mice, Inbred C57BL
Mice
Glaucoma
Linear Models
Perfusion
Intraocular Pressure
Male
General Science & Technology
Publication Status: Published
Article Number: e0150694
Online Publication Date: 2016-03-07
Appears in Collections:Bioengineering
Faculty of Engineering