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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Authors: | Wenhua Zheng Qian Meng Haitao Wang Fengxia Yan Peter J Little Xinguo Deng Shaofen Lin |
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Institution: | 1.Faculty of Health Sciences,University of Macau,Macau,China;2.State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou,China;3.School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,China;4.School of Pharmacy, Pharmacy Australia Centre of Excellence (PACE),The University of Queensland,Woolloongabba,Australia |
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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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