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R. Wong, I. Chowers, T.I. Dentchev, R.H. Farkas, T.L. Gunatilaka, P.A. Campochiaro, C.A. Curcio, D.J. Zack, J.L. Dunaief; The Iron Carrier Transferrin Is Upregulated in Retinas From Patients With Age–Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3017.
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Purpose: Iron can cause oxidative stress and elevated levels are associated with several neurodegenerative diseases. Transferrin (Tf) is an iron transport protein, carrying iron into cells after binding the cell surface transferrin receptor. In the retina, Tf is upregulated in the retinas of human and monkey eyes with glaucoma, with highest level expression in the Muller cells, suggesting that altered iron homeostasis could play a role in glaucoma. Similarly, iron is found in increased concentrations in AMD affected eyes. The aim of the current study is to quantify transferrin in AMD eyes compared to healthy age–matched controls. Methods: Postmortem retinas were obtained from AMD and healthy eyes. A custom human retina cDNA microarray was used to characterize gene expression patterns across 33 retinas from 19 unaffected donors and 12 retinas from 6 AMD patients (6 with neovascular and 6 with non–neovascular AMD). Regression model and false discovery rate (FDR) calculations were applied to identify age, gender, and AMD associated gene expression. Tf protein was assessed by semi–quantitative Western analysis and immunohistochemistry. Results: Mean transferrin mRNA levels detected by microarray were 1.4–fold higher in males compared to females, and 2.3–fold higher in AMD retinas compared to unaffected retinas. Semiquantitative Western analysis demonstrated a 2.1–fold increase in Tf protein in AMD eyes. Immunohistochemistry showed more intense and widespread Tf label in AMD maculas, particularly in large drusen, Muller cells, and photoreceptors. Conclusions: These data demonstrate that in AMD retinas, Tf expression is increased as compared to healthy controls. Combined with our earlier findings of 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/hephaestin knockout mice, these transferrin data provide additional evidence that altered iron homeostasis may play a role in the pathogenesis of AMD.
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