Physiology of aqueous humor production and intraocular pressure

Erwin Schrödinger Fellowship J 1866 Phsysiology of aeqous humor production and intraocular pressure Herbert REITSAMER 06.03.2000 Ocular hypertension is the most significant risc factor for glaucoma, and reduction of intraocular pressure (IOP) remains the primary goal of glaucoma treatment. The steady state IOP is set by aqueous production and outflow, and it is our knowledge of aqueous dynamics that provides a rational basis for understanding ocular hypertension and the various treatment modalities used to manipulate IOP. The goal of this project is to address a fundamental gap in our knowledge of aqueous dynamics: the role of ciliary blood flow in aqueous production. The project will test the hypothesis that, for a given level of secretory stimulation, aqueous production is blood flow dependent if blood flow falls, and that the known insensitivity of aqueous production to changes in perfusion pressure is due to ciliary blood flow autoregulation (i.e., the maintainance of flow despite changes in perfusion pressure). The project`s specific aims are to quantify the interrelationships between ciliary blood flow, metabolism and aqueous production over a wide range of perfusion pressures under control conditions and after administration of drugs expected to alter aqeous production or ciliary blood flow, or both. The experiments will be performed in anesthetized rabbits instrumented with hydraulic occluders on the inferior vena cava and aorta to control mean arterial pressure (MAP) which will be measured via an arterial canula. The eye will be cannulated to measure IOP. Ciliary and choroidal blood flow will be measured by laser Doppler flowmetry. Ciliary metabolism will be estimated form ciliary PO 2 , pH and transepithelial potential measurements. Aequous production will be measured by fluorophotometry. The standard protocol will entail holding the MAP at different levels above and below baseline until steady state conditions for measurements are achieved. The protocol will be performed initially in control animals to establish the normal relationships between the vasodilation and vasoconstriction. Plotting the aquwous flow as a function of ciliary blood flow will indicate which drugs alter aqeous production directly at cellular level, those that affect production indirectly due to vascular effects, and those that affect production directly and indirectly. This information will improve our understanding of the physiology underlying aqueous dynamics and the pharmacology of drugs currently used in the treatment of glaucoma, and also be used to continue the development of a comprehensive mathematical model of ocular hydrodynamics.