GDNF-induced osteopontin from Müller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration.
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GDNF-induced osteopontin from Müller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration. / Patricia, Del Río; Irmler, Martin; Arango-González, Blanca; Favor, Jack; Bobe, Caroline; Bartsch, Udo; Vecino, Elena; Beckers, Johannes; Hauck, Stefanie M; Ueffing, Marius.
in: GLIA, Jahrgang 59, Nr. 5, 5, 2011, S. 821-832.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - GDNF-induced osteopontin from Müller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration.
AU - Patricia, Del Río
AU - Irmler, Martin
AU - Arango-González, Blanca
AU - Favor, Jack
AU - Bobe, Caroline
AU - Bartsch, Udo
AU - Vecino, Elena
AU - Beckers, Johannes
AU - Hauck, Stefanie M
AU - Ueffing, Marius
PY - 2011
Y1 - 2011
N2 - Glial cell line-derived neurotrophic factor (GDNF) enhances the survival of a variety of neurons, including photoreceptors (PR) in the retina. In contrast to most other GDNF receptive neurons, GDNF does, however, not exert its neuroprotective activity directly on PR neurons but transmits it indirectly by inducing expression of yet unknown neurotrophic factors in retinal Müller glial (RMG) cells. Genome-wide differential transcriptome analyses of GDNF-treated mouse retinas revealed 30 GDNF-induced transcripts containing a total of six genes coding for secreted molecules. Among them was (OPN), a secreted glycoprotein which was expressed in mouse RMG and secreted from primary mouse RMG in culture. Furthermore, OPN secretion was significantly upregulated on GDNF treatment of primary RMG. To validate, whether OPN could qualify as a neuroprotective factor for PR, we evaluated its potential neurotrophic activity on isolated PR in vitro as well as on retinal explants from the retinal degeneration 1 (Pde6brd1) mouse mutant. OPN exerted a significant, positive survival effect on primary porcine PR cells in a concentration-dependent manner and induced activation of PI3K/Akt pro-survival pathway. Moreover, in retinal explant cultures from Pde6brd1 mice, OPN significantly reduced the percentage of apoptotic cells to levels comparable with that observed in explants from wild-type mice and led to survival of significantly more PR in long-term retinal explant cultures. Our findings suggest that RMG-derived OPN is a novel candidate protein that transmits part of the GDNF-induced neuroprotective activity of RMG to PR cells.
AB - Glial cell line-derived neurotrophic factor (GDNF) enhances the survival of a variety of neurons, including photoreceptors (PR) in the retina. In contrast to most other GDNF receptive neurons, GDNF does, however, not exert its neuroprotective activity directly on PR neurons but transmits it indirectly by inducing expression of yet unknown neurotrophic factors in retinal Müller glial (RMG) cells. Genome-wide differential transcriptome analyses of GDNF-treated mouse retinas revealed 30 GDNF-induced transcripts containing a total of six genes coding for secreted molecules. Among them was (OPN), a secreted glycoprotein which was expressed in mouse RMG and secreted from primary mouse RMG in culture. Furthermore, OPN secretion was significantly upregulated on GDNF treatment of primary RMG. To validate, whether OPN could qualify as a neuroprotective factor for PR, we evaluated its potential neurotrophic activity on isolated PR in vitro as well as on retinal explants from the retinal degeneration 1 (Pde6brd1) mouse mutant. OPN exerted a significant, positive survival effect on primary porcine PR cells in a concentration-dependent manner and induced activation of PI3K/Akt pro-survival pathway. Moreover, in retinal explant cultures from Pde6brd1 mice, OPN significantly reduced the percentage of apoptotic cells to levels comparable with that observed in explants from wild-type mice and led to survival of significantly more PR in long-term retinal explant cultures. Our findings suggest that RMG-derived OPN is a novel candidate protein that transmits part of the GDNF-induced neuroprotective activity of RMG to PR cells.
KW - Animals
KW - Immunohistochemistry
KW - Mice
KW - Enzyme-Linked Immunosorbent Assay
KW - Mice, Transgenic
KW - Blotting, Western
KW - In Situ Nick-End Labeling
KW - Apoptosis/drug effects/physiology
KW - Cell Survival/drug effects/physiology
KW - Glial Cell Line-Derived Neurotrophic Factor/metabolism/pharmacology
KW - Neuroglia/drug effects/metabolism/secretion
KW - Osteopontin/metabolism/pharmacology/secretion
KW - Photoreceptor Cells, Vertebrate/drug effects/metabolism
KW - Retinal Degeneration/metabolism
KW - Animals
KW - Immunohistochemistry
KW - Mice
KW - Enzyme-Linked Immunosorbent Assay
KW - Mice, Transgenic
KW - Blotting, Western
KW - In Situ Nick-End Labeling
KW - Apoptosis/drug effects/physiology
KW - Cell Survival/drug effects/physiology
KW - Glial Cell Line-Derived Neurotrophic Factor/metabolism/pharmacology
KW - Neuroglia/drug effects/metabolism/secretion
KW - Osteopontin/metabolism/pharmacology/secretion
KW - Photoreceptor Cells, Vertebrate/drug effects/metabolism
KW - Retinal Degeneration/metabolism
M3 - SCORING: Journal article
VL - 59
SP - 821
EP - 832
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 5
M1 - 5
ER -
