CD1 Mouse Retina Is Shielded From Iron Overload Caused by a High Iron Diet.
OBJECTIVE
High RPE iron levels have been associated with age-related macular degeneration. Mutation of the ferroxidase ceruloplasmin leads to RPE iron accumulation and degeneration in patients with aceruloplasminemia; mice lacking ceruloplasmin and its homolog hephaestin have a similar RPE degeneration. To determine whether a high iron diet (HID) could cause RPE iron accumulation, possibly contributing to RPE oxidative stress in AMD, we tested the effect of dietary iron on mouse RPE iron.


METHODS
Male CD1 strain mice were fed either a standard iron diet (SID) or the same diet with extra iron added (HID) for either 3 months or 10 months. Mice were analyzed with immunofluorescence and Perls' histochemical iron stain to assess iron levels. Levels of ferritin, transferrin receptor, and oxidative stress gene mRNAs were measured by quantitative PCR (qPCR) in neural retina (NR) and isolated RPE. Morphology was assessed in plastic sections.


RESULTS
Ferritin immunoreactivity demonstrated a modest increase in the RPE in 10-month HID mice. Analysis by qPCR showed changes in mRNA levels of iron-responsive genes, indicating moderately increased iron in the RPE of 10-month HID mice. However, even by age 18 months, there was no Perls' signal in the retina or RPE and no retinal degeneration.


CONCLUSIONS
These findings indicate that iron absorbed from the diet can modestly increase the level of iron deposition in the wild-type mouse RPE without causing RPE or retinal degeneration. This suggests regulation of retinal iron uptake at the blood-retinal barriers.
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States 2Albany Medical College, Albany, New York, United States.
Devang L
DL
Bhoiwala
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Ying
Y
Song
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Alyssa
A
Cwanger
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Esther
E
Clark
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States 3Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China.
Liang-liang
LL
Zhao
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States 3Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China.
Chenguang
C
Wang
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Yafeng
Y
Li
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Delu
D
Song
F. M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Joshua L
JL
Dunaief
D000818:Animals; D004195:Disease Models, Animal; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D019266:Iron, Dietary / Q000633:toxicity; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D019266:Iron, Dietary; D011990:Receptors, Transferrin; D012313:RNA; D007501:Iron