The oral iron chelator deferiprone protects against iron overload-induced retinal degeneration

Majda Hadziahmetovic, Ying Song, Natalie Wolkow, Jared Iacovelli, Steven Grieco, Jennifer Lee, Arkady Lyubarsky, Domenico Pratico, John Connelly, Michael Spino, Z. Leah Harris, Joshua L. Dunaief

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Purpose. Iron-induced oxidative stress may exacerbate age-related macular degeneration (AMD). Ceruloplasmin/Hephaes-tin double-knockout (DKO) mice with age-dependent retinal iron accumulation and some features of AMD were used to test retinal protection by the oral iron chelator deferiprone (DFP). Methods. Cultured retinal pigment epithelial (ARPE-19) cells and mice were treated with DFP. Transferrin receptor mRNA (Tfrc), an indicator of iron levels, was quantified by qPCR. In mice, retinal oxidative stress was assessed by mass spectrometry, and degeneration by histology and electroretinography. Results. DFP at 60 /xM decreased labile iron in ARPE-19 cells, increasing Tfrc and protecting 70% of cells against a lethal dose of H2O2. DFP 1 mg/mL in drinking water increased retinal Tfrc mRNA 2.7-fold after 11 days and also increased transferrin receptor protein. In DKOs, DFP over 8 months decreased retinal iron levels to 72% of untreated mice, diminished retinal oxidative stress to 70% of the untreated level, and markedly ameliorated retinal degeneration. DFP was not retina toxic in wild-type (WT) or DKO mice, as assessed by histology and electroretinography. Conclusions. Oral DFP was not toxic to the mouse retina. It diminished retinal iron levels and oxidative stress and protected DKO mice against iron overload-induced retinal degeneration. Further testing of DFP for retinal disease involving oxidative stress is warranted.

Original languageEnglish (US)
Pages (from-to)959-968
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number2
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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