We have previously identified a parasympathetic neural circuit in birds that is involved in the light-regulated control of choroidal blood flow (CBF). This circuit consists of: retina - suprachiasmatic nucleus (SCN) - medial subdivision of Edinger-Westphal nucleus (EWM) - choroidal neurons of ciliary ganglion - choroidal blood vessels. We have shown by lesions of EWM that neural control of CBF by this circuit is important for retinal health. We propose to further explore the neural substrates and functional significance of CBF control, primarily using pigeons as a model, but also carrying out anatomical studies on primate EW to enable future physiological studies of CBF in mammals. Four lines of study are proposed. In the first line, we will 1) use immunolabeling to determine the anatomical subdivisions of monkey EW using antisera against several neuropeptides, neurotransmitters and calcium-binding proteins (whose differential distributions define the subdivisions of avian EW); and 2) use pathway tracing techniques to determine the central inputs to the monkey correspondent of avian EWM. In the second line, we will further explore the role of EWM in CBF control in pigeons, by using: 1) immunohistochemical, pharmacological and physiological approaches to determine if the choroidal vasodilation mediated by EWM involves muscarinic mechanisms and the endothelial-dependent relaxing factor nitric oxide; and 2) several immunohistochemical and histochemical markers to identify the specific retinal cell types directly affected by loss of EWM-mediated adaptive control of CBF and determine the roles of hypoxia, metabolic insufficiency and ischemia in yielding retinal pathology after EWM lesions. In the third line, we will determine the specific role of SCN input to EWM and determine their relationship to the circadian system in pigeons, by using: 1) a combination of EM and LM immunohistochemical methods to characterize the retinal pathology that develops specifically after SCN lesions; 2) direct measurements of CBF in awake birds to determine if there is a circadian CBF rhythm; and 3) a pharmacological approach to explore the EWM-mediated effects of melatonin on CBF. Finally, in the fourth line, we will use anatomical (anterograde/retrograde pathway tracing and immunohistochemistry) and physiological techniques (microstimulation and CBF measurements) to determine the central circuitry subserving control of CBF via the facial nerve in pigeons. Neural control of CBF may play an important role in the adaptive support of the retina, particularly retinal photoreceptors. Aberrant neural control of CBF may contribute to degenerative processes in some diseases that affect the retina, such as senile macular disease, hypertension and diabetes. Understanding the role that neural control of CBF plays in support of the retina may further clarify how these diseases act to produce retinal damage and suggest preventive measures.
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