A sensitive ocular perfusion apparatus measuring outflow facility

Kee, Changwon; Hong, Taemin; Choi, Ayoung

doi:10.1076/ceyr.16.12.1198.5023

Cited by 10 publications

(6 citation statements)

References 2 publications

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“…The scaling relationship parallels differences in anterior chamber volume among these animals. 41 It is similar in scale but slightly smaller in value than prior measurements in rats ( C = 0.044 ± 0.010 μL/min/mm Hg 14 and 0.051 ± 0.010 μL/min/mm Hg 35 ). Both studies examined Lewis rats so the higher facility of this albino strain may reflect the absence of pigment granules, which can accumulate in the trabecular meshwork.…”

Section: Discussioncontrasting

confidence: 42%

“…Other variations of the method directly measure flow with a flowmeter and use a gravity feed to eliminate the pump and control circuitry. 33 – 35 The mCP technique was found to produce equivalent results as the CF technique in half the time. Moreover, C estimates were very consistent and were validated by inserting a shunt of known conductance into the eye.…”

Section: Discussionmentioning

confidence: 97%

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Aqueous Humor Dynamics of the Brown-Norway Rat

Ficarrotta

Bello

Mohamed

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeThe study aimed to provide a quantitative description of aqueous humor dynamics in healthy rat eyes.MethodsOne eye of 26 anesthetized adult Brown-Norway rats was cannulated with a needle connected to a perfusion pump and pressure transducer. Pressure-flow data were measured in live and dead eyes by varying pump rate (constant-flow technique) or by modulating pump duty cycle to hold intraocular pressure (IOP) at set levels (modified constant-pressure technique). Data were fit by the Goldmann equation to estimate conventional outflow facility (\begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}C\end{document}) and unconventional outflow rate (\begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}{F_{un}}\end{document}). Parameter estimates were respectively checked by inserting a shunt of similar conductance into the eye and by varying eye hydration methodology.ResultsRat IOP averaged 14.6 ± 1.9 mm Hg at rest. Pressure-flow data were repeatable and indistinguishable for the two perfusion techniques, yielding \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\bol...

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Section: Discussioncontrasting

confidence: 42%

Section: Discussionmentioning

confidence: 97%

Aqueous Humor Dynamics of the Brown-Norway Rat

Ficarrotta

Bello

Mohamed

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Feola et al [21] reported values of 21.2 [11.2, 40.0] and 26.1 [23.8, 28.7] nl�min -1 �mmHg -1 for young and middle-aged Brown Norway rats, respectively, while Ficarrotta et al [15] reported a value of 23 ± 2 nl�min -1 �mmHg -1 for retired-breeder Brown Norway rats. Facility values in this study (23 ± 4 nl�min -1 �mmHg -1 ) are within margin of error of their findings, and all are around two-fold less than reported values for albino rat species [37,38]. Moreover, repeated estimates of outflow facility in conscious rats exhibited similar variability as cited studies performed on different rats [15,21].…”

Section: Plos Onesupporting

confidence: 77%

A portable feedback-controlled pump for monitoring eye outflow facility in conscious rats

Mohamed

Passaglia

2023

PLoS ONE

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Intraocular pressure (IOP) is heavily influenced by the resistance of trabecular outflow pathways through which most of the aqueous humor produced by the eye continuously drains. The standard method of quantifying outflow resistance and other aspects of ocular fluid dynamics is eye cannulation, which allows for direct measurement and manipulation of IOP and flow in animal models. Since the method is invasive, indirect techniques that are slower and less accurate must be used for chronological studies. A novel technology is introduced that can autonomously measure outflow facility in conscious rats multiple times a day. A smart portable micropump infuses fluid into the eye through a permanently-implanted cannula and dynamically adjusts flow rate using a unique proportional feedback algorithm that sets IOP to a target level, even though IOP fluctuates erratically in awake free-moving animals. Pressure-flow data collected by the system from anesthetized rats were validated against intraocular recordings with commercial pressure and flow sensors. System and sensor estimates of outflow facility were indistinguishable, averaging 23 ± 3 nl·min-1·mmHg-1 across animals (n = 11). Pressure-flow data were then collected round-the-clock for several days from conscious rats, while outflow facility was measured every few hours. A significant diurnal facility rhythm was observed in every animal (n = 4), with mean daytime level of 22 ± 10 nl·min-1·mmHg-1 and mean nighttime level of 15 ± 7 nl·min-1·mmHg-1. The rhythm correlated with diurnal changes in IOP and likely contributed prominently to those changes based on the day-night swing in facility magnitude. Hence, the portable smart pump offers a unique tool for repeated long-term monitoring of outflow facility and other possible parameters of ocular health. It could also be useful in animal glaucoma studies for reversibly inducing acute or chronic ocular hypertension without explicitly damaging trabecular outflow pathways.

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“…The system was tested in the range of facilities relevant to human eyes (≈200 nl / min / mmHg ). Kee et al [ 34 ] proposed a modified version of this system in which a number of components added for accuracy were omitted in the interest of simplicity. They tested their system using rat eyes ( C ≈ 50 nl / min / mmHg ).…”

Section: Introductionmentioning

confidence: 99%

Measurement of Outflow Facility Using iPerfusion

et al. 2016

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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.

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A sensitive ocular perfusion apparatus measuring outflow facility

Abstract: Our perfusion apparatus is highly stable, sensitive, and capable of measuring subtle changes in outflow facility in vivo and in vitro.

Cited by 10 publications

References 2 publications

Aqueous Humor Dynamics of the Brown-Norway Rat

Aqueous Humor Dynamics of the Brown-Norway Rat

A portable feedback-controlled pump for monitoring eye outflow facility in conscious rats

Measurement of Outflow Facility Using iPerfusion

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