The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms.

Published online

Journal Article

PURPOSE: To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO3)-induced retinal degeneration and on the hereditary retinal degeneration caused by the rd6 mutation. METHODS: Retinas from NaIO3-treated C57BL/6J mice, with or without DFP cotreatment, were analyzed by histology, immunofluorescence, and quantitative PCR to investigate the effect of DFP on retinal degeneration. To facilitate photoreceptor quantification, we developed a new function of MATLAB to perform this task in a semiautomated fashion. Additionally, rd6 mice treated with or without DFP were analyzed by histology to assess possible protection. RESULTS: In NaIO3-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress-related gene heme oxygenase-1 and the complement gene C3. DFP treatment partially protected against NaIO3-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin (Rho) and retinal pigment epithelium-specific 65 kDa protein (Rpe65), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in rd6 mice. CONCLUSIONS: The oral iron chelator DFP provides significant protection against retinal degeneration induced through different modalities. This suggests that iron chelation could be useful as a treatment for retinal degeneration even when the main etiology does not appear to be iron dysregulation. TRANSLATIONAL RELEVANCE: These data provide proof of principle that the oral iron chelator DFP can protect the retina against diverse insults. Further testing of DFP in additional animal retinal degeneration models at a range of doses is warranted.

Full Text

Duke Authors

Cited Authors

  • Hadziahmetovic, M; Pajic, M; Grieco, S; Song, Y; Song, D; Li, Y; Cwanger, A; Iacovelli, J; Chu, S; Ying, G-S; Connelly, J; Spino, M; Dunaief, JL

Published Date

  • 2012

Published In

Volume / Issue

  • 1 / 3

Start / End Page

  • 2 -

PubMed ID

  • 24049709

Pubmed Central ID

  • 24049709

International Standard Serial Number (ISSN)

  • 2164-2591

Digital Object Identifier (DOI)

  • 10.1167/tvst.1.3.2

Language

  • eng

Conference Location

  • United States