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Marina G. Yefimova, Jean-Claude Jeanny, Nicole Keller, Claire Sergeant, Xavier Guillonneau, Carole Beaumont, Yves Courtois; Impaired Retinal Iron Homeostasis Associated with Defective Phagocytosis in Royal College of Surgeons Rats. Invest. Ophthalmol. Vis. Sci. 2002;43(2):537-545.
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purpose. To determine whether iron homeostasis disorder accompanies retinal
degeneration in Royal College of Surgeons (RCS) rats.
methods. The presence of iron was revealed directly by proton-induced x-ray
emission (PIXE) and indirectly by electron microscopy (EM). Ferritin,
transferrin (Tf), and transferrin receptor (Tf-R) were localized by
immunohistochemistry. Ferritin and Tf proteins were analyzed by Western
blot analysis. Comparative study of Tf-R content was performed by
slot-blot analysis and ferritin content was evaluated by enzyme-linked
immunosorbent assay (ELISA). Ferritin and Tf-R expression was studied
by reverse transcription–polymerase chain reaction (RT-PCR) and Tf
expression by in situ hybridization (ISH). All studies were performed
in RCS and control retinas from postnatal days (PN)20 to PN55.
results. PIXE analysis showed iron accumulation in outer retina of RCS rats in a
time-dependent manner. EM studies revealed irregular iron inclusions on
partially degenerated outer segments (OS) of photoreceptors and
lamellar whorls at PN35 and very large iron deposits on membranes from
a debris layer at PN55. No such deposits were found in the inner
retina. Ferritin and Tf-R expression and protein levels seemed to be
unaffected in the inner part of the retina. Iron accumulation was
preceded by Tf degradation, as revealed by immunohistochemistry and
Western blot analysis. Tf mRNA was detected in RCS rat retinal pigment
epithelium (RPE) at all stages studied.
conclusions. This study presents the first evidence for a correlation of iron
homeostasis imbalance with the neurodegenerative state of the retina in
RCS rats. The iron imbalance is not the underlying genetic defect but
is the result of impaired RPE–photoreceptor interaction, which leads
to debris accumulation and subsequent blockage of the outer retina’s
iron delivery pathway. The increase of iron in the photoreceptor area
may enhance the vulnerability of cells to oxidative
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