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Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes

Aqueous humor dynamics are commonly assessed by infusing fluid into the eye and measuring intraocular pressure (IOP). From the pressure-flow relationship, conventional outflow facility is estimated to study glaucomatous processes that lower facility or identify therapeutics that enhance facility in...

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Autores principales: Mohamed, Youssef, Passaglia, Christopher L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662726/
https://www.ncbi.nlm.nih.gov/pubmed/37988400
http://dx.doi.org/10.1371/journal.pone.0294607
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author Mohamed, Youssef
Passaglia, Christopher L.
author_facet Mohamed, Youssef
Passaglia, Christopher L.
author_sort Mohamed, Youssef
collection PubMed
description Aqueous humor dynamics are commonly assessed by infusing fluid into the eye and measuring intraocular pressure (IOP). From the pressure-flow relationship, conventional outflow facility is estimated to study glaucomatous processes that lower facility or identify therapeutics that enhance facility in hopes of restoring healthy IOP levels. The relative merits and limitations of constant flow (CF), gravity-driven constant pressure (CPg), and pump-driven constant pressure (CPp) infusion techniques were explored via simulations of a lumped parameter viscoelastic model of the eye. Model parameter values were based on published perfusion system properties and outflow facility data from rodents. Step increases in pressure or flow were simulated without and with IOP noise recorded from enucleated eyes, anesthetized animals, and conscious animals. Steady-state response levels were determined using published window and ratio criteria. Model simulations show that all perfusion techniques estimate facility accurately and that ocular fluid dynamics set a hard limit on how fast measurements can be taken. This limit can be approached with CPg and CPp systems by increasing their gain but not with CF systems, which invariably take longest to settle. Facility experiment duration is further lengthened by inclusion of IOP noise, and data filtering is needed for steady-state detection with in vivo noise. The ratio criterion was particularly affected because noise in the flow data is amplified by the higher gain of CPg and CPp systems. A recursive regression method is introduced, which can ignore large transient IOP fluctuations that interfere with steady-state detection by fitting incoming data to the viscoelastic eye model. The fitting method greatly speeds up data collection without loss of accuracy, which could enable outflow facility measurements in conscious animals. The model may be generalized to study response dynamics to fluid infusion in other viscoelastic compartments of the body and model insights extended to optimize experiment design.
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spelling pubmed-106627262023-11-21 Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes Mohamed, Youssef Passaglia, Christopher L. PLoS One Research Article Aqueous humor dynamics are commonly assessed by infusing fluid into the eye and measuring intraocular pressure (IOP). From the pressure-flow relationship, conventional outflow facility is estimated to study glaucomatous processes that lower facility or identify therapeutics that enhance facility in hopes of restoring healthy IOP levels. The relative merits and limitations of constant flow (CF), gravity-driven constant pressure (CPg), and pump-driven constant pressure (CPp) infusion techniques were explored via simulations of a lumped parameter viscoelastic model of the eye. Model parameter values were based on published perfusion system properties and outflow facility data from rodents. Step increases in pressure or flow were simulated without and with IOP noise recorded from enucleated eyes, anesthetized animals, and conscious animals. Steady-state response levels were determined using published window and ratio criteria. Model simulations show that all perfusion techniques estimate facility accurately and that ocular fluid dynamics set a hard limit on how fast measurements can be taken. This limit can be approached with CPg and CPp systems by increasing their gain but not with CF systems, which invariably take longest to settle. Facility experiment duration is further lengthened by inclusion of IOP noise, and data filtering is needed for steady-state detection with in vivo noise. The ratio criterion was particularly affected because noise in the flow data is amplified by the higher gain of CPg and CPp systems. A recursive regression method is introduced, which can ignore large transient IOP fluctuations that interfere with steady-state detection by fitting incoming data to the viscoelastic eye model. The fitting method greatly speeds up data collection without loss of accuracy, which could enable outflow facility measurements in conscious animals. The model may be generalized to study response dynamics to fluid infusion in other viscoelastic compartments of the body and model insights extended to optimize experiment design. Public Library of Science 2023-11-21 /pmc/articles/PMC10662726/ /pubmed/37988400 http://dx.doi.org/10.1371/journal.pone.0294607 Text en © 2023 Mohamed, Passaglia https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mohamed, Youssef
Passaglia, Christopher L.
Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes
title Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes
title_full Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes
title_fullStr Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes
title_full_unstemmed Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes
title_short Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes
title_sort simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662726/
https://www.ncbi.nlm.nih.gov/pubmed/37988400
http://dx.doi.org/10.1371/journal.pone.0294607
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