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Julia Arciero, Brendan Fry, Alice Chandra Verticchio Vercellin, Brent A Siesky, Alon Harris; Modeling conducted metabolic responses in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5012.
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© ARVO (1962-2015); The Authors (2016-present)
Observed relationships between hemodynamics and retinal function suggest that theoretical modeling of retinal blood flow provides a useful tool for identifying mechanisms that lead to flow impairments. Here, three variations of a conducted metabolic signal are simulated within a heterogeneous arteriolar network of the mouse retina to demonstrate key aspects of flow regulation.
A mathematical model of oxygen transport is extended here to include flow regulation in response to changes in pressure, shear stress, and oxygen demand. The metabolic signal (Si) is implemented as a wall-derived signal that reflects the oxygen deficit along the network. Three cases of conduction are considered: (i) no conduction (Si = 0); (ii) a constant signal (Si=S*); and (iii) a flow-weighted signal (Si ~ Qi/Qtotal), where Q represents flow.
Figures 1A and 1B show the model predicted values of average tissue PO2 and the fraction of tissue < 5 mmHg (tissue hypoxic fraction) for oxygen demand values of 1, 2, and 4 cm3 O2/100 cm3/min for each of the three cases. The average tissue PO2 is predicted to be highest (and tissue hypoxic fraction is predicted to be the lowest) when the signal at each outflowing vessel is weighted by the flow rate in the vessel. Figures 1C and 1D show average tissue PO2 and tissue hypoxic fraction as S* values are varied with and without flow-weighting. As S* is increased, there is a small increase in the average tissue PO2 and small decrease in tissue hypoxic fraction in all cases.
The model shows that the increases in average tissue PO2 due to flow-weighting are just as significant as if the entire level of signal is increased. This indicates that the heterogeneity of the downstream conducted responses serves to regulate flow better than a constant conducted response. Such theoretical work supports the importance of the non-uniform structure of the retinal vasculature when assessing the capability and/or dysfunction of blood flow regulation in the retinal microcirculation.
This is a 2020 ARVO Annual Meeting abstract.
Figure 1. (A) Average tissue PO2 and (B) tissue hypoxic fraction (< 5 mmHg) in the retinal arteriolar network as oxygen demand is varied. (C) Average tissue PO2 and (D) tissue hypoxic fraction (<5 mmHg) as the metabolic signal is varied (oxygen demand is 4 cm3 O2/100cm3/min). Three types of conducted response signals (no signal (blue), constant signal (red), or flow-weighted signal (black)) are depicted.
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