ironjustice@aol.com
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Joined: 28 Apr 2005
Posts: 1522
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 Posted: Mon May 08, 2006 11:34 pm Post subject:
Macular Degeneration / iron
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(Investigative Ophthalmology and Visual Science. 2006;47:2135-2140.)
© 2006 by The Association for Research in Vision and Ophthalmology,
Inc.
DOI: 10.1167/iovs.05-1135
The Iron Carrier Transferrin Is Upregulated in Retinas from Patients
with Age-Related Macular Degeneration
Itay Chowers,1 Robert Wong,2 Tzvete Dentchev,2 Ronald H. Farkas,3 Jared
Iacovelli,2 Tushara L. Gunatilaka,3 Nancy E. Medeiros,4 J. Brett
Presley,5 Peter A. Campochiaro,3,6 Christine A. Curcio,5 Joshua L.
Dunaief,2 and Donald J. Zack3,6,7,8
1From the Department of Ophthalmology, Hadassah-Hebrew University
Medical Center, Jerusalem, Israel; the 2F. M. Kirby Center for
Molecular Ophthalmology, Scheie Eye Institute, Philadelphia,
Pennsylvania; the 3Guerrieri Center for Genetic Engineering and
Molecular Ophthalmology, Wilmer Ophthalmological Institute, Department
of Ophthalmology, and 6Departments of Neuroscience and 7Molecular
Biology and Genetics, and the 8McKusick-Nathans Institute of Genetic
Medicine, The Johns Hopkins University School of Medicine, Baltimore,
Maryland; 4Retina Specialists of North Alabama, Huntsville, Alabama;
and the 5Department of Ophthalmology, University of Alabama,
Birmingham, Alabama.
PURPOSE. Iron can cause oxidative stress, and elevated iron levels have
been associated with several neurodegenerative diseases including
age-related macular degeneration (AMD). Transferrin, an iron transport
protein, is expressed at high levels in the retina. The purpose of this
study was to assess transferrin involvement in AMD by determining the
expression profile of transferrin in retinas with AMD compared with
retinas without evidence of disease.
METHODS. Postmortem retinas were obtained from AMD and non-AMD eyes.
Expression of transferrin was assessed in a microarray dataset from 33
retinas of unaffected donors and 12 retinas of patients with AMD (six
with neovascular AMD and six with non-neovascular AMD). Quantitative
real-time RT-PCR (QPCR) was used to confirm the microarray results.
Transferrin protein expression was assessed by semiquantitative Western
blot analysis and immunohistochemistry.
RESULTS. In comparison to unaffected retinas, mean transferrin mRNA
levels, as measured by microarray analysis were elevated 3.5- and
2.1-fold in non-neovascular and neovascular AMD retinas, respectively.
Semiquantitative Western blot analysis demonstrated a 2.1-fold increase
in transferrin protein in AMD eyes. Immunohistochemistry showed more
intense and widespread transferrin label in AMD maculas, particularly
in large drusen, Müller cells, and photoreceptors.
CONCLUSIONS. These data demonstrate that transferrin expression is
increased in the retinas of patients with AMD relative to those of
healthy control patients of comparable age. Along with previous studies
that have demonstrated elevated iron levels in AMD retinas, early onset
drusen formation in a patient with retinal iron overload resulting from
aceruloplasminemia, and retinal degeneration with some features of
macular degeneration in the iron-overloaded retinas of
ceruloplasmin/hephestin knockout mice, the present study suggests that
altered iron homeostasis is associated with AMD.
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