A2E-associated cell death and inflammation in retinal pigmented epithelial cells from human induced pluripotent stem cells - ScienceDirect

Stem Cell Research

Vipul M. Parmar¹ 

关键词: iPSC-RPE;    Lipofuscin;    A2E;    VEGF-A;    Inflammation;    A2E;    N-retinyl-N-retinylidene ethanolamine;    AMD;    age-related macular degeneration;    iPSC;    induced pluripotent stem cells;    RPE;    retinal pigmented epithelium;    KLF4;    kruppel-like factor 4;    OCT4;    octamer-binding transcription factor 4;    SOX2;    sex determining region Y-box 2;    c-MYC;    V-myc avian myelocytomatosis viral oncogene homolog;    CFH;    Complement factor H;    GAPDH;    glyceraldehyde 3- phosphate dehydrogenase;    VEGF;    vascular endothelial growth factor;   

DOI  :  10.1016/j.scr.2018.01.014

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

Accumulation of lipofuscin in the retinal pigmented epithelium (RPE) is observed in retinal degenerative diseases including Stargardt disease and age-related macular degeneration. Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) is a major component of lipofuscin. A2E has been implicated in RPE atrophy and retinal inflammation; however, mice with A2E accumulation display only a mild retinal phenotype. In the current study, human iPSC-RPE (hiPSC-RPE) cells were generated from healthy individuals to examine effects of A2E in human RPE cells. hiPSC-RPE cells displayed RPE-specific features, which include expression of RPE-specific genes, tight junction formation and ability to carry out phagocytosis. hiPSC-RPE cells demonstrated cell death and increased VEGF-A production in a time-dependent manner when they were cocultured with 10 μM of A2E. PCR array analyses revealed upregulation of 26 and 12 pro-inflammatory cytokines upon A2E and H2O2 exposure respectively, indicating that A2E and H2O2 can cause inflammation in human retinas. Notably, identified gene profiles were different between A2E- and H2O2- treated hiPSC-RPE cells. A2E caused inflammatory changes observed in retinal degenerative diseases more closely as compared to H2O2. Collectively, these data obtained with hiPSC-RPE cells provide evidence that A2E plays an important role in pathogenesis of retinal degenerative diseases in humans.

【 授权许可】

Unknown