The long term goal of the work proposed in this application is to understand how IOP and the rate of aqueous flow are regulated. The model to be used to further this goal is the circadian rhythm of IOP and aqueous flow in New Zealand White Rabbits. The goal of the experiments proposed is to identify the receptors, transmitters, and second messengers which mediate the circadian rhythms of IOP and aqueous flow in this animal model.
The specific aims of this proposal are: 1.to determine whether norepinephrine and specific beta-adrenergic agonists increase aqueous flow, 2. to determine whether alpha1- or alpha2-adrenergic receptors participate in controlling the. circadian rhythms of IOP and aqueous flow, 3. to measure the aqueous concentrations of transmitters and hormones which are potential mediators of the rhythms of IOP and aqueous flow, 4. to determine the role of cAMP, cGMP and IP3 in mediating the circadian rhythms of IOP and aqueous flow, 5. to determine whether the responsiveness of hormone receptors linked to cAMP, cGMP or IP3 production vary during the circadian cycle, 6. to determine the mechanism of the direct effect of light on TOP during the dark phase of the circadian cycle, 7. to seek evidence for an ocular """"""""clock"""""""" which participates in circadian control of IOP and flow in rabbits, 8. to further explore the possibility that melatonin, or other indoleamines, participate in control of the circadian rhythms of IOP and flow. Careful study of the temporal changes of IOP and aqueous flow in this animal model offers a unique opportunity to resolve some of the dilemmas which plague the field of aqueous dynamics. Elucidation of the endogenous mechanisms which control IOP and flow in this animal model is likely to advance our understanding of aqueous dynamics in humans and permit exploitation and manipulation of endogenous regulatory mechanisms in humans to achieve better control of elevated IOP in glaucoma patients.
