Iron upregulates melanogenesis in cultured retinal pigment epithelial cells

Exp Eye Res. 2014 Nov:128:92-101. doi: 10.1016/j.exer.2014.09.010. Epub 2014 Sep 30.

Abstract

The purpose of our studies was to examine the relationship between iron and melanogenesis in retinal pigment epithelial cells, as prior observations had suggested that iron may promote melanogenesis. This relationship has potential clinical importance, as both iron overload and hyperpigmentation are associated with age-related macular degeneration (AMD). Human fetal retinal pigment epithelial cells and ARPE-19 cells were treated with iron in the form of ferric ammonium citrate, after which quantitative RT-PCR and electron microscopy were performed. Melanogenesis genes tyrosinase, tyrosinase-related protein 1, Hermansky-Pudlak Syndrome 3, premelanosome protein and dopachrome tautomerase were upregulated, as was the melanogenesis-controlling transcription factor, microphthalmia-associated transcription factor (MITF). Iron-treated cells had increased pigmentation and melanosome number. Multiple transcription factors upstream of MITF were upregulated by iron.

Keywords: ARPE-19 cells; Human fetal retinal pigment epithelial cells; Iron; LEF 1; MITF; Melanosome; Retinal pigment epithelium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carrier Proteins / genetics
  • Cells, Cultured
  • Ferric Compounds / pharmacology*
  • Gestational Age
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Intramolecular Oxidoreductases / genetics
  • Melanins / biosynthesis*
  • Melanosomes / metabolism*
  • Membrane Glycoproteins / genetics
  • Monophenol Monooxygenase / genetics
  • Oxidoreductases / genetics
  • Quaternary Ammonium Compounds / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / embryology
  • Retinal Pigment Epithelium / metabolism
  • Tissue Donors
  • Up-Regulation / physiology*
  • gp100 Melanoma Antigen / genetics

Substances

  • Carrier Proteins
  • Ferric Compounds
  • HPS3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Melanins
  • Membrane Glycoproteins
  • PMEL protein, human
  • Quaternary Ammonium Compounds
  • RNA, Messenger
  • gp100 Melanoma Antigen
  • Oxidoreductases
  • TYRP1 protein, human
  • Monophenol Monooxygenase
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
  • ferric ammonium citrate