Related Experiment Video
Updated: Feb 15, 2026

Rapid, Directed Differentiation of Retinal Pigment Epithelial Cells from Human Embryonic or Induced Pluripotent Stem Cells
Published on: October 30, 2017
A2E-associated cell death and inflammation in retinal pigmented epithelial cells from human induced pluripotent stem
Vipul M Parmar1, Tanu Parmar1, Eisuke Arai1
1Department of Ophthalmology and Visual Sciences, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, United States.
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 10μM 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.
Related Concept Videos
Induced Pluripotent Stem Cells
Induced Pluripotent Stem Cells
Somatic...
Embryonic Stem Cells
Adult Stem Cells
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...

