Purchase this article with an account.
S.M. Hauck, N. Kinkl, C.A. Deeg, M. Swiatek–de Lange, S. Schöffmann, M. Ueffing; GDNF Family Ligands Trigger Indirect Neuroprotective Signaling in Retinal Glial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2053.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Apoptotic cell death of photoreceptors is the final event leading to blindness in the heterogeneous group of inherited retinal degenerations. GDNF was found to rescue photoreceptor function and survival very effectively in an animal model of retinal degeneration (Frasson et al., 1999). In this study we aimed at elucidating the as of yet unresolved cellular mechanism of GDNF action.
GDNF–receptor expression was investigated by RT–PCR and by immunolabeling. GDNF–induced signaling was investigated on isolated retinal Mueller glial cells (RMG) and differential gene expression was evaluated by northern blot and ELISA.
We show here that in porcine retina, GDNF–receptors GFRα–1 and RET are expressed on RMG but not on photoreceptors. Additionally, RMG express the receptors for the GFL family members Artemin and Neurturin (GFRα–2 and GFRα–3). GDNF, Artemin and Neurturin induced signaling in isolated primary RMG resulted in activation of three intracellular cascades: MEK/ERK, SAPK and PKB/AKT pathways, wirh different kinetics in dependence of stimulating GFL. We correlate the findings to intact porcine retina, where GDNF induces ERK phosphorylation in perinuclear regions of RMG located in the inner nuclear layer. GDNF signaling resulted in transcriptional upregulation of bFGF, which in turn was found to support photoreceptor survival in vitro.
We provide a detailed model for GDNF–induced signaling in mammalian retina and propose that GDNF–induced rescue effects on mutated photoreceptors is an indirect effect mediated by retinal Mueller glial cells.
This PDF is available to Subscribers Only