The long-term objective of this project is to systematically investigate the regulation of choroidal blood flow and the role of the choroid in ocular pressure homeostasis. Ischemic damage is thought to be the underlying cause of blindness in ocular diseases such as diabetic retinopathy and glaucoma. Because the choroid is the primary source of oxygen and nutrients for the retina, knowledge of choroidal blood flow regulation is essential for understanding, preventing and treating the vascular consequences of these and other diseases. In contrast to the previous view of the choroid as a passive vascular bed devoid of autoregulatory ability, studies during the past funding period show that choroidal blood flow is well autoregulated, particularly when arterial pressure is the manipulated variable. Moreover, the results indicate that the mechanism responsible for choroidal autoregulation is myogenic rather than metabolic (as in the retina), and that it acts to control choroidal blood volume and so minimize the fluctuations in intraocular pressure that would otherwise occur during normal variations in arterial blood pressure. The present project will continue to examine the regulation of choroidal blood flow by testing the following hypotheses: 1) a myogenic mechanism regulates the flow and volume of blood in the choroid, 2) the myogenic mechanism is modulated by neurohumoral factors, and 3) the myogenic mechanism plays a significant role in intraocular pressure homeostasis. A mathematical model based on these hypotheses serves as the conceptual framework for the project and as a dynamic 'library' for the project's results. Although the model was refined significantly during the last funding period, quantitative information for many of the model's key variables and relationships must still be obtained. To achieve this goal, the project's specific aims are: 1) to quantitate the neural and humoral control of choroidal blood flow to determine the normal myogenic set-point and the physiologic variables that modulate it, and 2) to determine the role of the choroid in intraocular pressure by determining the factors that affect choroidal blood volume. The work will be conducted in anesthetized animals instrumented to control and monitor arterial and intraocular pressures while measuring choroidal blood flow by laser-Doppler flowmetry. Most of the experiments will involve the systematic manipulation of arterial and intraocular pressures before and after selective blockade or stimulation of known vascular effector systems to quantify their effects on the choroidal pressure-flow relation and intraocular pressure. The experimental results will be used to continue refining the mathematical model so that the model accurately portrays the regulation of choroidal blood flow and its role in ocular pressure homeostasis upon completion of the project.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences C Study Section (VISC)
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University of Texas Health Science Center San Antonio
Schools of Medicine
San Antonio
United States
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Emeterio Nateras, Oscar San; Harrison, Joseph M; Muir, Eric R et al. (2014) Choroidal blood flow decreases with age: an MRI study. Curr Eye Res 39:1059-67
Bogner, Barbara; Runge, Christian; Strohmaier, Clemens et al. (2014) The effect of vasopressin on ciliary blood flow and aqueous flow. Invest Ophthalmol Vis Sci 55:396-403
Strohmaier, Clemens A; Reitsamer, Herbert A; Kiel, Jeffrey W (2013) Episcleral venous pressure and IOP responses to central electrical stimulation in the rat. Invest Ophthalmol Vis Sci 54:6860-6
Lavery, W J; Kiel, J W (2013) Effects of head down tilt on episcleral venous pressure in a rabbit model. Exp Eye Res 111:88-94
Shih, Yen-Yu I; Wang, Lin; De La Garza, Bryan H et al. (2013) Quantitative retinal and choroidal blood flow during light, dark adaptation and flicker light stimulation in rats using fluorescent microspheres. Curr Eye Res 38:292-8
Li, Guang; Kiel, Jeffrey W; Cardenas, Damon P et al. (2013) Postocclusive reactive hyperemia occurs in the rat retinal circulation but not in the choroid. Invest Ophthalmol Vis Sci 54:5123-31
Li, Guang; Shih, Yen-Yu Ian; Kiel, Jeffrey W et al. (2013) MRI study of cerebral, retinal and choroidal blood flow responses to acute hypertension. Exp Eye Res 112:118-24
Shih, Yen-Yu I; Li, Guang; Muir, Eric R et al. (2012) Pharmacological MRI of the choroid and retina: blood flow and BOLD responses during nitroprusside infusion. Magn Reson Med 68:1273-8
De La Garza, Bryan H; Muir, Eric R; Shih, Yen-Yu I et al. (2012) 3D magnetic resonance microscopy of the ex vivo retina. Magn Reson Med 67:1154-8
Lavery, William J; Muir, Eric R; Kiel, Jeffrey W et al. (2012) Magnetic resonance imaging indicates decreased choroidal and retinal blood flow in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci 53:560-4

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