Neuroprotective effects of glial mediators in interactions between retinal neurons and Müller cells.

Abstract 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 Muller cells, have been shown to promote RGC survival. Assuming that the communication of RGCs with Muller cells involves a release of glioactive substances we sought to determine whether retinal neurons are able to modulate expression levels of Muller cell-derived PEDF, VEGF and IL-6. We demonstrate elevated mRNA levels of these factors in Muller cells in co-cultures with RGCs or R28 cells when compared to homotypic Muller cell cultures. Furthermore, R28 cells were more protected from apoptosis when co-cultured with Muller cells. IL-6 and VEGF were upregulated in Muller 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 Muller cells to increase production of neuroprotective factors, which counteract RGC apoptosis.