The long term goal of my work is to understand how aqueous flow and IOP are regulated. The circadian rhythm of IOP in rabbits represents a non-invasive animal model for generating reproducible and predictable changes in IOP, and recent work showing the importance of changes in aqueous flow in the circadian rhythm of IOP establish the ciliary processes as the target organ for the rhythm of IOP. The work proposed in this application is intended to identify the ciliary process hormone receptors which mediate the rhythm of aqueous flow, to establish the role of ciliary process cyclic nucleotides in regulation of the rhythm of aqueous flow, and to determine the role of the adrenergic innervation to the eye in the rhythm of flow.
The specific aims proposed are: 1. to determine the effect on the circadian rhythm of flow of cervical ganglionectomy and decentralization of the cervical ganglion, 2. to explore the role of the guanyl nucleotide binding proteins Ns and Ni in the circadian rhythm of flow and IOP using cholera and pertussis toxins, 3. to examine the effects of specific receptor antagonists and agonists on flow and IOP at different times during the circadian cycle, 4. to determine whether there is a circadian rhythm in the ciliary processes of atrial natriuretic factor, vasoactive intestinal peptide or somatostatin which could participate in mediation of the rhythm of flow and IOP, 5. to determine whether the sensitivities of receptors linked to cyclic AMP and cyclic GMP production vary during the circadian cycle. IOP in humans is recognized to show a daily rhythm which can be exaggerated in glaucoma patients, and this """"""""spontaneous variation of IOP in open-angel glaucoma remains one of the most important and least understood enigmas of glaucoma"""""""". A better understanding of the mechanisms underlying the circadian rhythm of aqueous flow in this rabbit model may permit exploitation and manipulation of normal regulatory mechanisms to achieve control of IOP in glaucoma patients.