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

该项目旨在阐明视网膜中神经元到胶质细胞和神经胶质细胞到神经元信号的核苷酸信号机制，作为一个名副其实的中枢神经系统的模型系统。我们和其他人已经证明，多种核苷酸受体由视网膜神经元和神经胶质细胞以细胞类型特异性和发育调节的模式表达。我们还表明，不同的核苷酸受体参与了视网膜功能细胞间的信号传递，例如对神经元活动做出反应的神经胶质体积调节。基于这些结果，并利用包括双光子显微镜在内的各种分子生物学、药理学、免疫细胞化学、电生理和荧光技术，我们想要研究核苷酸受体在(I)突触周围和血管周围神经胶质细胞在发育、成熟神经元活动和视网膜损伤过程中的体积调节，(Ii)神经胶质细胞迁移和增殖的诱导和方向，以及(Iii)小胶质细胞和视网膜神经节细胞在生理性细胞死亡过程中的相互作用。将使用几种视网膜损伤的动物模型(糖尿病、视网膜缺血/再灌注)、转基因小鼠和器官组织培养。这些结果将有助于更好地了解核苷酸受体的功能以及视网膜生理和病理的功能，以及在糖尿病视网膜病变和视网膜水肿等视网膜疾病中的新的治疗策略。

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.