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Jan D Unterlauft, Helena Savkovic-Cvijic, Peter MH Wiedemann, Wolfram Eichler; Pigment Epithelium-Derived Factor of Glial Origin enhances Survival of Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5835.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal neurodegeneration secondary to diabetic and hypertensive retinopathy and glaucoma can lead to irreversible loss of vision and is today among the leading causes of blindness worldwide. Our purpose was to show that pigment epithelium-derived factor (PEDF), secreted by the retinal pigment epithelium and Müller glial cells (MGC), exerts neuroprotective and neurotrophic actions towards retinal ganglion cells (RGC) in a cell culture model.
Homotypic and co-culture experiments using immunoisolated primary RGC and cultured Müller glial cells were conducted for 24 hours under normoxic (95% air; 5% CO2) and hypoxic conditions (0% O2; 5% CO2; 95% N2). PEDF was substituted to homotypic RGC cultures or depleted from RGC/MGC co-cultures by adding appropriate antibodies or by pretreatment of MGC with appropriate small interfering RNA (siRNA) directed against PEDF encoding RNA.
After 24 hours of normoxic treatment RGC survival rate was 54.04±0.03% in homotypic and 68.52±0.03% in co-cultures (p<0.05). Corresponding hypoxic survival rates were 32.84±0.02% in homotypic and 44.83±0.02% in co-cultures (p<0.01). Supplementing PEDF in homotypic cultures led to a significant increase of surviving RGC both under normoxic and hypoxic conditions. PEDF depletion in co-cultures by added antibodies or pretreatment of MGC with siRNA against PEDF led to a significant decrease of RGC survival rate again under normoxic and hypoxic culture conditions.
Glia-derived PEDF exerts neuroprotective/ neurotrophic actions towards RGC in cell culture. Further experiments are needed to reveal the underlying mode of action and to prove the effectiveness of PEDF in a mammalian model.
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