The objectives of this proposal are to study neural and pharmacological controls of aqueous humor dynamics. Neural mechanisms will investigate the ocular effects of neuropeptides (pancreatic polypeptide, vasoactive intestinal polypeptide, etc.) and physiological regulators of aqueous humor dynamics. These agents will be studied via peripheral (topical, intracameral, intravitreal) and central (third ventricle and hypothalamic microinjection) routes of administration. Neural pathways are to be investigated by ablation of the superior cervical ganglion, greater superficial petrosal nerve and trigeminal nerve. Pharmacological controls will study ocular carbonic anhydrase with special attention to topically active inhibitory agents; the intraocular pressure lowering effect of topical dopamine as well as the effect of specific dopamine receptor (DA1 and DA2) agonists and antagonists; and the intraocular pressure effect of topical cannabinoid compounds. Aqueous humor dynamics will include intraocular pressure, outflow facility, episcleral venous pressure, aqueous humor flow, and ocular blood flow and volume. These studies relate to the regulation of intraocular pressure. The results will provide information on the role of neuropeptides as physiological regulators of aqueous humor dynamics and may provide clues about the underlying pathophysiology of glaucoma. Pharmacological modulation of intraocular pressure will provide insight into normal aqueous humor physiology and possibly new glaucoma therapeutic agents.
