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IGF-1-Mediated Survival from Induced Death of Human Primary Cultured Retinal Pigment Epithelial Cells Is Mediated by an Akt-Dependent Signaling Pathway

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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.

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Acknowledgements

This research was financially supported by the Guangdong Provincial Project of Science and Technology (2011B050200005), the National Natural Science Foundation of China (31371088), SRG2015-00004-FHS and MYRG2016-00052-FHS from University of Macau, and the Science and Technology Development Fund (FDCT) of Macao (FDCT 021/2015/A1 and FDCT 016/2016/A1).

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Authors and Affiliations

  1. Faculty of Health Sciences, University of Macau, Room 4021, Building E12, Avenida de Universidade, Taipa, Macau, China

    Wenhua Zheng, Qian Meng, Haitao Wang & Fengxia Yan

  2. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China

    Wenhua Zheng, Xinguo Deng & Shaofen Lin

  3. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China

    Haitao Wang

  4. School of Pharmacy, Pharmacy Australia Centre of Excellence (PACE), The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Australia

    Peter J. Little

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  1. Wenhua Zheng
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  2. Qian Meng
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  3. Haitao Wang
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  4. Fengxia Yan
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Correspondence to Wenhua Zheng.

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Wenhua Zheng, Qian Meng, and Haitao Wang contributed equally to this work.

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Zheng, W., Meng, Q., Wang, H. et al. IGF-1-Mediated Survival from Induced Death of Human Primary Cultured Retinal Pigment Epithelial Cells Is Mediated by an Akt-Dependent Signaling Pathway. Mol Neurobiol 55, 1915–1927 (2018). https://doi.org/10.1007/s12035-017-0447-0

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  • DOI: https://doi.org/10.1007/s12035-017-0447-0

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