Dysfunction of the retinal pigment epithelium with age: increased iron decreases phagocytosis and lysosomal activity Huiyi Chen 1*, Thomas J Lukas 2, Nga Du 1, Genn Suyeoka 1, and Arthur H. Neufeld 1 1 Ophthalmology, Northwestern University School of Medicine, Chicago, Illinois, United States 2 Ophthalmology, Northwestern University, Chicago, Illinois, United States * To whom correspondence should be addressed. E-mail: huiyi- [email][/email]. Abstract PURPOSE. Iron accumulation with age in the retinal pigment epithelium (RPE) may be one important source of oxidative stress that contributes to age- related macular degeneration (AMD). We compared young and old rodent RPE/choroid to assess iron homeostasis during normal aging and the effects of increased iron on the functions of RPE cells. METHODS. The iron level, mRNA expression and protein level of iron regulatory molecules in RPE/choroid were quantitatively compared between young and old animals. To test effects of increased intracellular iron on the functions of RPE cells, in vitro ARPE-19 cells were treated with high iron and assessed for phagocytosis activity and lysosomal activity. RESULTS. The level of iron was significantly increased in the aged RPE/choroid. Ferritin and ceruloplasmin mRNAs were significantly increased in the aged RPE/choroid; whereas, transferrin, transferrin receptor and ferroportin mRNAs did not change with age. At the protein level, decreased transferrin and transferrin receptor, increased ferritin and ceruloplasmin, and unchanged ferroportin were observed in the aged RPE/ choroids. Exposure of ARPE-19 cells to increased iron markedly decreased phagocytosis activity, interrupted cathepsin D processing and reduced the cathepsin D activity in RPE cells. CONCLUSIONS. In the RPE/choroid of old animals, there are iron accumulation and associated alterations in iron homeostasis. The iron accumulation with age may impair the phagocytosis and lysosomal functions of RPE cells in the aged RPE/choroid. Therefore, age-related changes of iron homeostasis in the RPE could increase the susceptibility of the tissue to genetic mutations associated with AMD. Key Words: age-related macular degeneration, oxidative damage, ARPE-19 P<P, published online ahead of print January 17, 2009 (Investigative Ophthalmology and Visual Science. ) DOI: 10.1167/iovs.08-2850 Copyright © 2009 by the Association for Research in Vision and Ophthalmology Who loves ya. Tom Jesus Was A Vegetarian! [URL]http://tinyurl.com/2r2nkh[/URL] Man Is A Herbivore! [URL]http://tinyurl.com/4rq595[/URL] DEAD PEOPLE WALKING [URL]http://tinyurl.com/zk9fk[/URL]
