Purpose: This study uses a theoretical model to investigate the response of retinal blood flow to changes in tissue oxygen demand. The study is motivated by the need for a better understanding of metabolic flow regulation mechanisms in health and disease.
Methods: A mathematical model is used to calculate retinal blood flow for different levels of tissue oxygen demand in the presence or absence of regulatory mechanisms. The model combines a compartmental view of the retinal vasculature and a Krogh cylinder description for oxygen delivery to retinal tissue.
Results: The model predicts asymmetric behavior in response to changes in tissue oxygen demand. When all regulatory mechanisms are active, the model predicts a 6% decrease in perfusion when tissue oxygen demand is decreased by 50% and a 23% increase in perfusion when tissue oxygen demand is increased by 50%. In the absence of metabolic and carbon dioxide responses, the model predicts a constant level of blood flow that does not respond to changes in oxygen demand, suggesting the importance of these two response mechanisms. The model is not able to replicate the increase in oxygen venous saturation that has been observed in some flicker stimulation studies.
Conclusions: The increase in blood flow predicted by the model due to an increase in oxygen demand is not in the same proportion as the change in blood flow observed with the same decrease in oxygen demand, suggesting that vascular regulatory mechanisms may respond differently to different levels of oxygen demand. These results might be useful for interpreting clinical and experimental findings in health and disease.
Julia Arciero, Alon Harris, Brent Siesky, Annahita Amireskandari, Victoria Gershuny, Aaron Pickrell, and Giovanna Guidoboni. Theoretical analysis of vascular regulatory mechanisms contributing to retinal blood flow autoregulationmechanisms contributing to retinal autoregulation. Investigative Ophthalmology & Visual Science, 54(8):5584– 5593, 2013.
Simone Cassani, Alon Harris, Brent Siesky, and Julia Arciero. Theoretical analysis of the relationship between changes in retinal blood flow and ocular perfusion pressure. Journal of Coupled Systems and Multiscale Dynamics, 3(1):38–46, 2015.
Paola Causin, Giovanna Guidoboni, Francesca Malgaroli, Riccardo Sacco, and Alon Harris. Blood flow mechanics and oxygen transport and delivery in the retinal microcirculation: multiscale mathematical modeling and numerical simulation. Biomechanics and Modeling in Mechanobiology, pages 1–18, 2015.
Stephen J Cringle and Dao-Yi Yu. A multi-layer model of retinal oxygen supply and consumption helps explain the muted rise in inner retinal po2 during systemic hyperoxia. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 132(1):61–66, 2002.
Guido T Dorner, Gerhard Garh ̈ofer, Karl H Huemer, Charles E Riva, Michael Wolzt, and Leopold Schmetterer. Hyperglycemia affects flicker-induced vasodilation in the retina of healthy subjects. Vision Research, 43(13):1495–1500, 2003.
G Garhofer, C Zawinka, H Resch, KH Huemer, GT Dorner, and L Schmetterer. Diffuse luminance flicker increases blood flow in major retinal arteries and veins. Vision Research, 44(8):833–838, 2004.
G Garhofer, C Zawinka, H Resch, P Kothy, L Schmetterer, and GT Dorner. Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes. British Journal of Ophthalmology, 88(7):887–891, 2004.
Henry Gray. Anatomy of the human body. Lea & Febiger, 1918.
Giovanna Guidoboni, Alon Harris, Lucia Carichino, Yoel Arieli, and Brent A Siesky. Effect of intraocular pressure on the hemodynamics of the central retinal artery: a mathematical model. Mathematical Biosciences and Engineering: MBE, 11(3):523–546, 2014.
Giovanna Guidoboni, Alon Harris, Simone Cassani, Julia Arciero, Brent Siesky, Annahita Amireskandari, Leslie Tobe, Patrick Egan, Ingrida Januleviciene, and Joshua
Park. Intraocular pressure, blood pressure, and retinal blood flow autoregulation: A mathematical model to clarify their relationship and clinical relevanceeffects of iop,
bp, and ar on retinal hemodynamics. Investigative Ophthalmology & Visual Science, 55(7):4105–4118, 2014.
Martin Hammer, Walthard Vilser, Thomas Riemer, Fanny Liemt, Susanne Jentsch, Jens Dawczynski, and Dietrich Schweitzer. Retinal venous oxygen saturation increases by flicker light stimulation. Investigative Ophthalmology & Visual Science, 52(1):274–277, 2011.
Sveinn Hakon Hardarson, Samy Basit, Thora Elisabet Jonsdottir, Thor Eysteinsson, Gisli Hreinn Halldorsson, Robert Arnar Karlsson, James Melvin Beach, Jon Atli Benediktsson, and Einar Stefansson. Oxygen saturation in human retinal vessels is higher in dark than in light. Investigative Ophthalmology & Visual Science, 50(5):2308–2311,2009.
D Liu, NB Wood, N Witt, AD Hughes, SA Thom, and XY Xu. Computational analysis of oxygen transport in the retinal arterial network. Current Eye Research, 34(11):945–956, 2009.
Aleksandra Mandecka, Jens Dawczynski, Marcus Blum, Nicolle Muller, Christoph Kloos, Gunter Wolf, Walthard Vilser, Heike Hoyer, and Ulrich Alfons Muller. Influence of flickering light on the retinal vessels in diabetic patients. Diabetes Care, 30(12):3048–3052, 2007.
Magnus W Roos. Theoretical estimation of retinal oxygenation during retinal artery occlusion. Physiological Measurement, 25(6):1523, 2004.
Yen-Yu I Shih, Lin Wang, Bryan H De La Garza, Guang Li, Grant Cull, Jeffery W Kiel, and Timothy Q Duong. Quantitative retinal and choroidal blood flow during light, dark adaptation and flicker light stimulation in rats using fluorescent microspheres. Current Eye Research, 38(2):292–298, 2013.
Pang-yu Teng, Justin Wanek, Norman P Blair, and Mahnaz Shahidi. Response of inner retinal oxygen extraction fraction to light flicker under normoxia and hypoxia in ratinner retinal oxygen extraction fraction. Investigative Ophthalmology & Visual Science, 55(9):6055–6058, 2014.
Norbert D Wangsa-Wirawan and Robert A Linsenmeier. Retinal oxygen: fundamental and clinical aspects. Archives of Ophthalmology, 121(4):547–557, 2003.