The studies proposed in this application are designed to 1. determine whether the circadian rhythm of IOP reflects a circadian rhythm of aqueous formation, 2. explore the neural and humoral pathways which mediate regulation of this rhythm of IOP, and 3. identify biochemical mechanisms which underlie the local, ocular mediation of the circadian rhythm of IOP in this animal model. The section on Glaucoma and Aqueous Dynamics of this department is committed to the long term goal of understanding the anatomic, physiologic and biochemical basis for regulation and maintenance of IOP and aqueous flow. The circadian rhythm of IOP represents a non-invasive technique for manipulating aqueous dynamics, and, as such, provides a """"""""handle"""""""" for studying mechanisms involved in variation of IOP. Better understanding of these mechanisms which mediate the circadian rhythm of IOP may further our understanding of the mechanisms which maintain and regulate the steady state of IOP. IOP in humans is recognized to show a daily rhythm which can be exaggerated in glaucoma patients. This spontaneous variation of IOP in open-angle glaucoma remains one of the most important and least understood enigmas of glaucoma, and a better understanding of the mechanisms underlying this phenomenon may permit exploitation of normal physiologic mechanisms to achieve control of IOP in glaucoma patients. This animal model for the circadian rhythm of IOP may also prove to be a useful non-invasive model for evaluating potential drugs for glaucoma therapy.
