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Majda Hadziahmetovic, Miroslav Pajic, Steven Grieco, Ying Song, Delu Song, Yafeng Li, Alyssa Cwanger, Jared Iacovelli, Sally Chu, Gui-shuang Ying, John Connelly, Michael Spino, Joshua L Dunaief; The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms. Trans. Vis. Sci. Tech. 2012;1(3):2. doi: https://doi.org/10.1167/tvst.1.3.2.
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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.
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.
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.
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.
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