[Protective Effects of Müller Glia Cells Towards Retinal Ganglion Cells]. / Der protektive Einfluss Müllerʼscher Gliazellen auf retinale Ganglienzellen.

INTRODUCTION: Müller glial cells carry out different tasks to warrant normal retinal functions. The aim of this study was to investigate if Müller cells also support retinal ganglion cells (RGC). MATERIALS AND METHODS: RGC were cultured for 24 hours in the presence or absence of Müller glial cells under normoxic (20% O2, 5% CO2) or hypoxic (0.2% O2, 5% CO2, 94.8% N2) culture conditions. The number of vital RGC and the length of the newly developed neurites were evaluated. RESULTS: Under normoxic conditions, RGC vitality was significantly higher (p < 0.01) when cultured with Müller cells (62.85 ± 2.06%) than without (47.29 ± 2.83%). Under hypoxia, RGC vitality was significantly higher (p < 0.01) in co-cultures (41.07 ± 2.28%) than in homotypic RGC cultures (28.49 ± 2.16%). The maximum length of the newly developed neurites was found in the normoxic co-culture (90.7 ± 7.4 µm), but showed only a minor difference (p = 0.04) when compared to the normoxic homotypic RGC culture. CONCLUSION: Müller glial cells support RGC under normoxic and hypoxic culture conditions. Length of newly developed neurites and number of surviving RGC are both parameters to evaluate cell vitality.

Müller Cell-Derived PEDF Mediates Neuroprotection via STAT3 Activation.

Background/ Aims: This study was performed to reveal signaling pathways exploited by pigment epithelium-derived factor (PEDF) derived from retinal (glial) Müller cells to protect retinal ganglion cells (RGCs) from cell death. METHODS: The survival of RGCs was determined in the presence of conditioned culture media (MCM) from or in co-cultures with Müller cells. The significance of PEDF-induced STAT3 activation was evaluated in viability assays and using Western blotting analyses and siRNA-transfected cells. RESULTS: Secreted mediators of Müller cells increased survival of RGCs under normoxia or hypoxia to a similar degree as of PEDF- or IL-6-exposed cells. PEDF and MCM induced an increased STAT3 activation in RGCs and R28 cells, and neutralization of PEDF in MCM attenuated STAT3 activation. Inhibition of STAT3 reduced PEDF-promoted survival of RGCs. Similar to IL-6, PEDF induced STAT3 activation, acting in a dose-dependent manner via the PEDF receptor (PEDF-R) encoded by the PNPLA2 gene. Ablation of PEDF-R attenuated MCM-induced STAT3 activation and compromised the viability of PEDF-exposed R28 cells. CONCLUSIONS: Müller cells are an important source of PEDF, which promotes RGC survival through STAT3 activation and, at least in part, via PEDF-R. Enhancing the secretory function of Müller cells may be useful to promote RGC survival in retinal neurodegenerative diseases.