Neuroprotective effects of glial mediators in interactions between retinal neurons and Müller cells. (August 2021)

• Record Type: Journal Article
• Authors: Zwanzig, Annette; Meng, Jie; Müller, Heidi; Bürger, Susanne; Schmidt, Manuela; Pankonin, Maik; Wiedemann, Peter; Unterlauft, Jan Darius; Eichler, Wolfram
• Is Part Of: Experimental eye research. Volume 209(2021)
• Publication Date: 2021-08
• Subjects: Neuroprotection -- Retina -- Neuron-glia interactions -- Apoptosis; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2021.108689
• Languages: English
• ISSNs: 0014-4835

Abstract

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 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. Highlights: There is a crosstalk between retinal neurons and glial (Müller) cells mediated through secreted mediators. This crosstalk contributes to maintaining expression of neuroprotective factors by Müller cells. PEDF, VEGF and IL-6 protect retinal neurons from apoptosis. Levels of VEGF and IL-6 in Müller cells increase in co-cultures with retinal ganglion cells (RGCs) or R28 cells. RGCs, via own mediators, can resist a demise by stimulating Müller cells to increase their production of protective factors.