Expression, function and interaction of purinergic receptor subtypes on glial cells of the retina

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The project is aimed at the elucidation of nucleotide signaling mechanisms involved in neuron-to-glia and glia-to-neuron signaling in the retina as a veritable model system of the CNS. We and others have shown that a variety of nucleotide receptors is expressed by retinal neurons and glial cells, in a cell type-specific and developmentally regulated pattern. We also have shown that distinct nucleotide receptors are involved in functional cell-to-cell signaling of the retina, such as glial volume regulation in response to neuronal activity. Based upon these results and using a variety of molecular biological, pharmacological, immunocytochemical, electrophysiological, and fluorimetric techniques including 2-photon microscopy, we want to study the involvement of nucleotide receptors in (i) the volume regulation of perisynaptic and perivascular glial cells processes during development, mature neuronal activity, and retinal injuries, (ii) the induction and direction of glial cell migration and proliferation, and (iii) the interactions between microglia and retinal ganglion cells during physiological cell death of the latter. Several animal models of retinal injuries (diabetes, retinal ischemia / reperfusion), transgenic mice, and organotypic tissue cultures will be employed. The results will contribute to a better understanding of the functions of nucleotide receptors and of retina physiology and pathology, as well as to novel therapeutic strategies in retinal diseases such as diabetic retinopathy and retinal edema.