Dataset Information

Differences in Outflow Facility Between Angiographically Identified High- Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine Eyes.

ABSTRACT:

Purpose

To investigate differences in outflow facility between angiographically determined high- and low-flow segments of the conventional outflow pathway in porcine eyes.

Methods

Porcine anterior segments (n = 14) were mounted in a perfusion chamber and perfused using Dulbecco's phosphate buffered solution with glucose. Fluorescein angiography was performed to determine high- and low-flow regions of the conventional outflow pathways. The trabecular meshwork (TM) was occluded using cyanoacrylate glue, except for residual 5-mm TM areas that were either high or low flow at baseline, designating these eyes as "residual high-flow" or "residual low-flow" eyes. Subsequently, outflow was quantitatively reassessed and compared between residual high-flow and residual low-flow eyes followed by indocyanine green angiography.

Results

Fluorescein aqueous angiography demonstrated high-flow and low-flow regions. Baseline outflow facilities were 0.320 ± 0.08 and 0.328 ± 0.10 µL/min/mmHg (P = 0.676) in residual high-flow and residual low-flow eyes before TM occlusion, respectively. After partial trabecular meshwork occlusion, outflow facility decreased to 0.209 ± 0.07 µL/min/mmHg (-32.66% ± 19.53%) and 0.114 ± 0.08 µL/min/mmHg (-66.57% ± 23.08%) in residual high- and low-flow eyes (P = 0.035), respectively. There was a significant difference in the resulting IOP increase (P = 0.034).

Conclusions

Angiographically determined high- and low-flow regions in the conventional outflow pathways differ in their segmental outflow facility; thus, there is an uneven distribution of local outflow facility across different parts of the TM.

SUBMITTER: Strohmaier CA

PROVIDER: S-EPMC10043501 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Differences in Outflow Facility Between Angiographically Identified High- Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine Eyes.

Strohmaier Clemens A CA McDonnell Fiona S FS Zhang Xiaowei X Wanderer Daniel D Stamer W Daniel WD Weinreb Robert N RN Huang Alex S AS

Investigative ophthalmology & visual science 20230301 3

<h4>Purpose</h4>To investigate differences in outflow facility between angiographically determined high- and low-flow segments of the conventional outflow pathway in porcine eyes.<h4>Methods</h4>Porcine anterior segments (n = 14) were mounted in a perfusion chamber and perfused using Dulbecco's phosphate buffered solution with glucose. Fluorescein angiography was performed to determine high- and low-flow regions of the conventional outflow pathways. The trabecular meshwork (TM) was occluded usin ...[more]

PMID: 36939719

Similar Datasets

Project 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.

Project description: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.

Dataset Information

Differences in Outflow Facility Between Angiographically Identified High- Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine Eyes.

Purpose

Methods

Results

Conclusions

Publications

Differences in Outflow Facility Between Angiographically Identified High- Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine Eyes.

Similar Datasets

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