The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms.
OBJECTIVE
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 therd6mutation.


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,rd6mice 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 geneC3. 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 inrd6mice.


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.


CONCLUSIONS
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.
F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA.
Majda
M
Hadziahmetovic
Miroslav
M
Pajic
Steven
S
Grieco
Ying
Y
Song
Delu
D
Song
Yafeng
Y
Li
Alyssa
A
Cwanger
Jared
J
Iacovelli
Sally
S
Chu
Gui-Shuang
GS
Ying
John
J
Connelly
Michael
M
Spino
Joshua L
JL
Dunaief
deferiprone; iron; retinal degeneration