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Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration
Zhang, J.1,2,3; Bai, Y.1,2,3; Huang, L.1,2,3; Qi, Y.1,2,3; Zhang, Q.1,2,3; Li, S.1,2,3; Wu, Y.4; Li, X.1,2,3
刊名CELL DEATH & DISEASE
2015-11-01
DOI10.1038/cddis.2015.330
6
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]RAPAMYCIN ; DISEASE ; HEALTH ; RPE ; BISRETINOIDS ; PATHOGENESIS ; INHIBITION ; ACTIVATION ; MECHANISMS ; PRODUCTS
英文摘要

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial (RPE) cells is a crucial causative factor responsible for the onset and progression of AMD. A2E, a major component of toxic lipofuscin implicated in AMD, is deposited in RPE cells with age. However, the mechanism whereby A2E may contribute to the pathogenesis of AMD remains unclear. We demonstrated that A2E was a danger signal of RPE cells, which induced autophagy and decreased cell viability in a concentration-and time-dependent manner. Within 15 min after the treatment of RPE with 25 mu M A2E, the induction of autophagosome was detected by transmission electron microscopy. After continuous incubating RPE cells with A2E, intense punctate staining of LC3 and increased expression of LC3-II and Beclin-1 were identified. Meanwhile, the levels of intercellular adhesion molecule (ICAM), interleukin (IL) 1 beta, IL2, IL-6, IL-8, IL-17A, IL-22, macrophage cationic peptide (MCP)-1, stromal cell-derived factor (SDF)-1, and vascular endothelial growth factor A (VEGFA) were elevated. The autophagic inhibitor 3-methyladenine (3-MA) and activator rapamycin were also used to verify the effect of autophagy on RPE cells against A2E. Our results revealed that 3-MA decreased the autophagosomes and LC3 puncta induced by A2E, increased inflammation-associated protein expression including ICAM, IL1 beta, IL2, IL-6, IL-8, IL-17A, IL-22, and SDF-1, and upregulated VEGFA expression. Whereas rapamycin augmented the A2E-mediated autophagy, attenuated protein expression of inflammation-associated and angiogenic factors, and blocked the Akt/mTOR pathway. Taken together, A2E induces autophagy in RPE cells at the early stage of incubation, and this autophagic response can be inhibited by 3-MA or augmented by rapamycin via the mTOR pathway. The enhancement of autophagy has a protective role in RPE cells against the adverse effects of A2E by reducing the secretion of inflammatory cytokines and VEGFA.

语种英语
WOS记录号WOS:000367155300011
项目编号Z131102000413004 ; 2015M570901 ; 2011CB510200 ; 81470649 ; 81271018
资助机构Beijing Nova Program ; China Postdoctoral Science Foundation ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China
引用统计
被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51306
专题北京大学第二临床医学院_眼科
北京大学基础医学院
北京大学第二临床医学院_药剂科
北京大学临床肿瘤学院_肝胆胰外二科
作者单位1.Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China
2.Minist Educ, Key Lab Vis Loss & Restorat, Beijing 100044, Peoples R China
3.Beijing Key Lab Diag & Treatment Retinal & Choroi, Beijing 100044, Peoples R China
4.Xiamen Univ, Eye Inst, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen 361102, Fujian Provine, Peoples R China
推荐引用方式
GB/T 7714
Zhang, J.,Bai, Y.,Huang, L.,et al. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration[J]. CELL DEATH & DISEASE,2015,6.
APA Zhang, J..,Bai, Y..,Huang, L..,Qi, Y..,Zhang, Q..,...&Li, X..(2015).Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration.CELL DEATH & DISEASE,6.
MLA Zhang, J.,et al."Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration".CELL DEATH & DISEASE 6(2015).
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