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

Published

Journal Article

Iron-induced oxidative stress may exacerbate age-related macular degeneration (AMD). Ceruloplasmin/Hephaestin 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).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.DFP at 60 μM decreased labile iron in ARPE-19 cells, increasing Tfrc and protecting 70% of cells against a lethal dose of H(2)O(2). 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.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.

Full Text

Duke Authors

Cited Authors

  • Hadziahmetovic, M; Song, Y; Wolkow, N; Iacovelli, J; Grieco, S; Lee, J; Lyubarsky, A; Pratico, D; Connelly, J; Spino, M; Harris, ZL; Dunaief, JL

Published Date

  • February 16, 2011

Published In

Volume / Issue

  • 52 / 2

Start / End Page

  • 959 - 968

PubMed ID

  • 21051716

Pubmed Central ID

  • 21051716

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

International Standard Serial Number (ISSN)

  • 0146-0404

Digital Object Identifier (DOI)

  • 10.1167/iovs.10-6207

Language

  • eng