Elevated intraocular pressure (IOP), is the most significant risk factor for glaucoma, and IOP reduction 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 high IOP and the various treatments used to manipulate IOP.
The goal of our research is to address a fundamental gap in our knowledge of aqueous dynamics: the role of ciliary blood flow in aqueous production. We are currently testing the hypothesis that a critical level of ciliary blood flow exists for a given level of secretory stimulation, and that aqueous production is blood flow independent until blood flow is reduced below that critical level. Our 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 aqueous production or ciliary blood flow, or both.
Our experiments are performed in anesthetized animals instrumented with hydraulic occluders on the inferior vena cava and aorta to control mean arterial pressure (MAP) which is measured via an arterial cannula. The eye is cannulated to measure IOP. Ciliary blood flow is measured by laser Doppler flowmetry using a fiber optic probe placed on the sclera over the ciliary body. Ciliary metabolism is estimated from ciliary PO2 measurements. Episcleral and anterior uveal venous pressures are measured by the servonull technique. Aqueous production is measured by fluorophotometry.
A typical experiment entails changing ciliary blood flow by holding the MAP at different levels above and below baseline for 60-90 min to obtain steady state measurements. We have already established the normal relationships between the measured variables, and are now looking at conditions of drug-induced secretory stimulation and inhibition, and ciliary vasodilation and vasoconstriction. Plotting the aqueous flow as a function of ciliary blood flow indicates which drugs alter aqueous production directly at the cellular level, those that affect production indirectly due to their vascular effects, and those that affect production directly and indirectly. This information will further our understanding of the physiology of aqueous dynamics and the pharmacology of drugs used in the treatment of glaucoma, and will also be used to continue the development of a comprehensive mathematical model of ocular hydrodynamics.
For more information, please contact:
Jeffrey W. Kiel, Ph.D.
Professor / Director of the Vascular Physiology Lab
UT San Antonio
7703 Floyd Curl Drive, MC 6230
San Antonio, TX 78229-3900