Effects of glial mediators on PEDF-mediated signaling and neuronal survival in the retina

点击翻译按钮获取中文摘要

Neuroprotective effects mediated by Müller glial cells may be of key importance for the development of retinal diseases such as glaucoma and diabetic retinopathy. Müller cells secrete survival-promoting mediators that protect neurons from cell death. This project seeks to explore mechanisms of action exerted by Müller cell-derived pigment-epithelium-derived factor (PEDF), which are involved in the survival of retinal ganglion cells (RGCs) under cellular stress conditions such as hypoxia/ ischemia. Experiments will be performed to determine underlying mechanisms of intracellular signal transduction, aimed to assess whether Müller cell-derived survival factors such as vascular endothelial growth factor (VEGF) and interleukin-6 interfere with PEDF-mediated neuroprotection. The proposed experiments will help to clarify the significance of PEDF-induced NF-kB and STAT3 signaling for the viability of RGCs under influence of Müller cell-derived secretions. Given that anti-VEGF drugs have been approved for therapy of angioproliferative retinal eye diseases this project will shed light on whether VEGF blockade affects Müller cell-promoted survival of RGCs. The results expected will contribute to understand the interplay of individual glial neuroprotective survival factors in the retina and will allow new insights into the status of the Müller cell as a potential target for future therapeutic anti-neurodegenerative treatment strategies.