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

神经胶质细胞介导的神经保护作用可能在青光眼和糖尿病视网膜病变等视网膜疾病的发展中起关键作用。meller细胞分泌促进生存的介质，保护神经元免于细胞死亡。本项目旨在探索<s:1> ller细胞衍生色素上皮衍生因子（PEDF）的作用机制，PEDF参与视网膜神经节细胞（RGCs）在缺氧/缺血等细胞应激条件下的存活。实验将确定细胞内信号转导的潜在机制，旨在评估<s:1>细胞源性生存因子，如血管内皮生长因子（VEGF）和白细胞介素-6是否干扰pedf介导的神经保护。本实验将有助于阐明pedf诱导的NF-kB和STAT3信号对<s:1> ller细胞衍生分泌物影响下RGCs存活的意义。鉴于抗VEGF药物已被批准用于血管增殖性视网膜眼病的治疗，该项目将揭示VEGF阻断是否影响<s:1> ller细胞促进的rgc存活。预期的结果将有助于理解视网膜中单个胶质神经保护存活因子的相互作用，并将使人们对<s:1>勒细胞作为未来抗神经退行性治疗策略的潜在靶点的地位有新的认识。

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.