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The Iron Carrier Transferrin Is Upregulated in Retinas from Patients with Age-Related Macular Degeneration

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.

This article has been cited by other articles:

				J. L. Dunaief Iron Induced Oxidative Damage As a Potential Factor in Age-Related Macular Degeneration: The Cogan Lecture Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4660 - 4664. [Abstract] [Full Text] [PDF]