title: IGF-1-Mediated Survival from Induced Death of Human Primary Cultured Retinal Pigment Epithelial Cells Is Mediated by an Akt-Dependent Signaling Pathway.
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.
authors.affiliation: Faculty of Health Sciences, University of Macau, Room 4021, Building E12, Avenida de Universidade, Taipa, Macau, China. wenhuazheng@umac.mo.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. wenhuazheng@umac.mo.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Faculty of Health Sciences, University of Macau, Room 4021, Building E12, Avenida de Universidade, Taipa, Macau, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Faculty of Health Sciences, University of Macau, Room 4021, Building E12, Avenida de Universidade, Taipa, Macau, China.|School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Faculty of Health Sciences, University of Macau, Room 4021, Building E12, Avenida de Universidade, Taipa, Macau, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Pharmacy Australia Centre of Excellence (PACE), The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shaofen
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D058449:Intravitreal Injections; D010775:Photic Stimulation / Q000009:adverse effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; Cell signaling; Growth factors; Retinopathy; Serum deprivation