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

Purpose: To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO)-induced retinal degeneration and on the hereditary retinal degeneration caused by the mutation.

Methods: Retinas from NaIO-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, mice treated with or without DFP were analyzed by histology to assess possible protection.

Results: In NaIO-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress-related gene heme oxygenase-1 and the complement gene . DFP treatment partially protected against NaIO-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin () and retinal pigment epithelium-specific 65 kDa protein (), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in 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.