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

Vipul M. Parmar, Tanu Parmar, Eisuke Arai, Lindsay Perusek, Akiko Maeda

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish (US)
Pages95-104
Number of pages10
JournalStem Cell Research
Volume27
DOIs
StatePublished - Mar 1 2018

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Induced Pluripotent Stem Cells
Cell Death
Epithelial Cells
Inflammation
Epithelium
Retinal Diseases
Lipofuscin
Ethanolamine
Tight Junctions
Retinoids
Macular Degeneration
Phagocytosis
Vascular Endothelial Growth Factor A
Genes
Atrophy
Retina
Up-Regulation
Cytokines
Phenotype
Polymerase Chain Reaction

Keywords

  • A2E
  • Inflammation
  • iPSC-RPE
  • Lipofuscin
  • VEGF-A

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

A2E-associated cell death and inflammation in retinal pigmented epithelial cells from human induced pluripotent stem cells. / Parmar, Vipul M.; Parmar, Tanu; Arai, Eisuke; Perusek, Lindsay; Maeda, Akiko.

In: Stem Cell Research, Vol. 27, 01.03.2018, p. 95-104.

Research output: Contribution to journalArticle

Parmar, Vipul M. ; Parmar, Tanu ; Arai, Eisuke ; Perusek, Lindsay ; Maeda, Akiko. / A2E-associated cell death and inflammation in retinal pigmented epithelial cells from human induced pluripotent stem cells. In: Stem Cell Research. 2018 ; Vol. 27. pp. 95-104.
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