Leipzig University, Department of Ophthalmology and Eye Hospital, Liebigstrasse 10-14, D-04103 Leipzig, Germany.
Leipzig University, Department of Ophthalmology and Eye Hospital, Liebigstrasse 10-14, D-04103 Leipzig, Germany.
Exp Eye Res. 2021 Aug;209:108689. doi: 10.1016/j.exer.2021.108689. Epub 2021 Jul 1.
Progressive retinal ganglion cell (RGC) loss underlies a number of retinal neurodegenerative disorders, which may lead to permanent vision loss. However, secreted neuroprotective factors, such as PEDF, VEGF and IL-6, which are produced by Müller cells, have been shown to promote RGC survival. Assuming that the communication of RGCs with Müller cells involves a release of glioactive substances we sought to determine whether retinal neurons are able to modulate expression levels of Müller cell-derived PEDF, VEGF and IL-6. We demonstrate elevated mRNA levels of these factors in Müller cells in co-cultures with RGCs or R28 cells when compared to homotypic Müller cell cultures. Furthermore, R28 cells were more protected from apoptosis when co-cultured with Müller cells. IL-6 and VEGF were upregulated in Müller cells under hypoxia. Both cytokines, as well as PEDF, induced an altered neuronal expression of members of the Bcl-2 family, which are central molecules in the regulation of apoptosis. These results suggest that in retinal ischemia, via own secreted mediators, RGCs can resist a potential demise by stimulating Müller cells to increase production of neuroprotective factors, which counteract RGC apoptosis.
进行性视网膜神经节细胞（RGC）丢失是许多视网膜神经退行性疾病的基础，可能导致永久性视力丧失。然而，已证实由 Muller 细胞产生的分泌性神经保护因子，如 PEDF、VEGF 和 IL-6，可以促进 RGC 存活。假设 RGC 与 Muller 细胞的通讯涉及神经活性物质的释放，我们试图确定视网膜神经元是否能够调节 Muller 细胞衍生的 PEDF、VEGF 和 IL-6 的表达水平。我们发现在与 RGC 或 R28 细胞共培养时 Muller 细胞中这些因子的 mRNA 水平升高，与同质 Muller 细胞培养相比。此外，当与 Muller 细胞共培养时，R28 细胞对细胞凋亡的保护作用更强。Muller 细胞在缺氧条件下上调 IL-6 和 VEGF。这两种细胞因子以及 PEDF 诱导了 Bcl-2 家族成员在神经元中的表达发生改变，Bcl-2 家族成员是调节细胞凋亡的核心分子。这些结果表明，在视网膜缺血时，通过自身分泌的介质，RGC 可以通过刺激 Muller 细胞增加神经保护因子的产生来抵抗潜在的死亡，从而对抗 RGC 凋亡。
