The proposed research focuses on the aqueous humor circulatory system of the human eye. Methods will be developed and employed to measure the rate of circulation of aqueous humor in the human eye under a variety of circumstances in order to determine its physiological regulation, its circadian rhythms, its response to disease, and its responsiveness to ocular hypotensive drugs. The techniques for study are non-invasive and safe, depending on the measurement of steady-state fluorescence of exogenous fluoroprobes, as well as other properties including polarization of fluorescence, spectra of fluorescence, and excited state lifetime of fluorescence. Studies of normal eyes and a number of clinical disorders including cystic fibrosis, diabetes insipidus, glaucoma, diabetes mellitus, central retinal vein occlusion, and uveitis will be made to characterize the characteristics and responsiveness of the aqueous circulation in these disorders. Studies of a number of pharmacological agents will be conducted including those whose effects are mediated via cyclic nucleotides, calcium channels, angiotensin, and polyphosphoinositides to gain general principles about the pharmacologic responsiveness of this circulatory system.
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