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 diseases. The current view of the choroid is that it is a passive vascular bed devoid of autoregulatory ability. However, this conclusion is based on the linear pressure-flow relation obtained when the perfusion pressure is decreased by raising the intraocular pressure. Studies in this laboratory show that elevated intraocular pressure is not the appropriate stimulus to elicit autoregulation in the choroid, and that choroidal blood flow is well autoregulated when arterial pressure is the manipulated variable. Moreover, by controlling the choroidal blood flow (and presumably blood volume), the mechanism responsible for choroidal autoregulation also regulates intraocular pressure. Therefore, this project will re-examine the issue of choroidal blood flow regulation 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 regulating intraocular pressure. Based on these hypotheses, a mathematical model of the choroid has been created to serve as the conceptual framework for the project. Because quantitative information for many of the model's key variables and relationships is not available in the literature, verifying the model's qualitative assumptions and reconciling its inconsistencies provide a logical basis for the project's specific aims which are: 1) to quantitate the local, neural and humoral control of choroidal blood flow to determine the normal myogenic set-point and the physiologic variables that modulate it, 2) to determine the role of the choroid in intraocular pressure by quantitating the compliances of the choroid and the ocular chambers, by measuring the vascular pressure gradients within the choroid, and by determining the factors that effect choroidal blood volume, and 3) to assess the effect of ocular hypertension on choroidal blood flow regulation in an animal model of glaucoma (i.e., trabecular obstruction) and to develop an animal model of glaucoma by shifting the myogenic set-point. All of the experiments will be conducted in anesthetized, albino rabbits artificially respired with room air and appropriately instrumented to control and monitor arterial and intraocular pressure while measuring choroidal blood flow by laser-Doppler flowmetry. The results of each series of experiments will be used to refine the mathematical model so that upon completion of the project the model will accurately portray the regulation of choroidal blood .flow and its role in ocular pressure homeostasis.
| 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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