Anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush are PI3K/AKT-dependent.
Exp Eye Res
; 90(5): 537-45, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20144610
ABSTRACT
The purpose of present study is to dissect the role of PI3K/AKT signaling in the anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on rat retinal ganglion cells (RGCs) after optic nerve (ON) crush. The ONs of seventy-two adult male Wistar rats were crushed by a standardized method. Control eyes received a sham operation. G-CSF or phosphate-buffered saline (PBS) was immediately administrated after the ON event for 5 days. Twelve rats were used to investigate the signaling pathways using western blot analysis. In other sixty rats, each eye also received intravitreal injections of PI3K/AKT inhibitor (LY294002) or PBS immediately after the experiments. Rats were euthanized at 1 or 2 weeks after the experiment. RGC density was counted by retrograde labeling with Fluorogold. Western blot analysis of p-AKT, TUNEL assays, and immunohistochemistry of the retinas were conducted. Two weeks after ON injury, RGC densities in the central and mid-peripheral retinas of ON-crushed, G-CSF treated rats were significantly higher than those of corresponding ON-crushed, G-CSF-treated and LY294002-injected rats (survival rates of 60% vs. 39% and 43% vs. 33%, respectively; p < 0.01). Decreased TUNEL staining and the up-regulations of p-AKT signaling in retinas of ON-crushed, G-CSF-treated rats were blocked by intravitreal injections of LY294002. The double staining showed that p-AKT expression co-localized with RGCs in the ON crushed, G-CSF treated retinas. In conclusion, the anti-apoptotic effects of G-CSF on RGCs are PI3K/AKT signaling dependent in the retinas to rescue RGCs after ON crush injury.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Ganglionares da Retina
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Fator Estimulador de Colônias de Granulócitos
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Fármacos Neuroprotetores
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Fosfatidilinositol 3-Quinases
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Traumatismos do Nervo Óptico
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Proteína Oncogênica v-akt
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Proteínas Reguladoras de Apoptose
Limite:
Animals
Idioma:
En
Revista:
Exp Eye Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Taiwan