The research objective is to demonstrate that the adrenergic nerves in the ciliary processes have a regulatory function in ciliary epithelial secretion of aqueous humor. Aqueous humor formation rate, intraocular pressure, and anterior chamber volume will be measured non-invasively using fluorophotometry, tonometry and photogrammetrically. Pharmacological studies will involve changing the activity of the ciliary epithelial cells with drugs that stimulate or block their post-junctional receptors. Neurotransmitter release from the sympathetic nerves in the ciliary processes will be stimulated and inhibited using drugs that interact with receptors on the sympathetic nerve terminals. Neurophysiological studies will investigate the effects of chronic stimulation of the cervical sympathetic nerves and of ganglionectomy on aqueous humor flow. The effects of beta-adrenergic desensitization and supersensitivity on ciliary epithelial secretion will be studied. Ciliary epithelial cells internalize plasma membrane in response to stimulation with beta-adrenergic drugs (eg. isoproterenol). This internalization of membrane is probably moving receptors into the cell and may be part of the desensitization mechanism. Using electrical stimulation of the sympathetic nerves and transmission electron microscopy, we will investigate whether endogenous norepinephrine from in situ sympathetic nerves induces plasma membrane internalization and if this is associated with a decrease in aqueous humor formation. The health-related goal of this research is to define the cell biology and pharmacology of the ciliary epithelium and identify parameters regulating secretion of aqueous humor that are pharmacologically manipulatable. Thus, glaucoma-related ocular hypertension can be medically managed and vision loss and surgery prevented.
