IGF-1-mediated survival from induced death of human primary cultured retinal pigment epithelial cells is mediated by an Akt-dependent signaling pathway

Zheng, Wenhua, Meng, Qian, Wang, Haitao, Yan, Fengxia, Little, Peter J., Deng, Xinguo and Lin, Shaofen (2017) IGF-1-mediated survival from induced death of human primary cultured retinal pigment epithelial cells is mediated by an Akt-dependent signaling pathway. Molecular Neurobiology, 1-13. doi:10.1007/s12035-017-0447-0


Author Zheng, Wenhua
Meng, Qian
Wang, Haitao
Yan, Fengxia
Little, Peter J.
Deng, Xinguo
Lin, Shaofen
Title IGF-1-mediated survival from induced death of human primary cultured retinal pigment epithelial cells is mediated by an Akt-dependent signaling pathway
Journal name Molecular Neurobiology   Check publisher's open access policy
ISSN 1559-1182
0893-7648
Publication date 2017-02-25
Sub-type Article (original research)
DOI 10.1007/s12035-017-0447-0
Open Access Status Not yet assessed
Start page 1
End page 13
Total pages 13
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract Degeneration of the human retinal pigmented epithelium (hRPE) is involved in several eye disorders such as age-related macular degeneration (AMD). In this study, we investigated the protective effect of IGF-1 on human primary cultured RPE cells and its underlying mechanism. IGF-1 dose- and time-dependently promoted the survival of RPE cells from serum deprivation. Western blot showed that IGF-1 stimulated the activation of the PI3K/Akt and MAPK pathways in hRPE. Inhibition of the PI3K/Akt pathway by the PI3K-specific inhibitor, LY294002 or inhibition of Akt by Akt-specific inhibitors Akt inhibitor VIII or SN-38, or downregulation Akt with siRNA specific for Akt blocked the effect of IGF-1 on hRPE. In contrast, blockade of the MAPK pathway with a specific inhibitor PD98059 had no effect. Interestingly, vitreous IGF-1 injection reversed the inhibitory effect of light exposure (a dry AMD model) on both a wave and b wave. Immunocytochemistry showed that vitreous IGF-1 injections promoted the survival of RPE cells in rat retina and the expression of RPE65 in RPE cells from light injury. These results indicate that IGF-1 is able to protect hRPE cell from different insults in vivo and in vitro. Further detailed studies may lead the way to a therapeutic intervention for retinal diseases in which cell death is an underlying contributory mechanism.
Keyword Apoptosis
Cell signaling
Growth factors
Retinopathy
Serum deprivation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Pharmacy Publications
 
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