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- W52700281 abstract "AbstractAge-related macular degeneration (AMD), a leading cause of blindness in the elderly, is thought to be in part an inflammatory disease involving dysregulation of the complement system. The photooxidative environment in the retina facilitates the formation of oxidative modifications that contribute to the accumulation of cellular debris such as lipofuscin within the retinal pigment epithelium (RPE) and drusen on Bruch’s membrane. A host of oxidative modifications have been found in AMD tissues, including carboxymethyllysine (CML), pentosidine, carboxyethylpyrrole (CEP), nitrotyrosine, 8-hydroxydeoxyguanosine, levuglandin/isolevuglandin-phosphatidyl ethanolamine hydroxylactams, and other adducts involving iso[4]levuglandin E2, hydroxynonenal, and acrolein. Oxidative modifications also generate oxidation-associated molecular patterns recognized by pattern-recognition receptors such as the complement system, the receptor for advanced glycation end products (RAGE), and the toll-like receptors. CML is a strong activator of RAGE, colocalizes with RAGE in AMD ocular tissues, is elevated in AMD plasma, and stimulates expression of vascular endothelial growth factor (VEGF) and angiogenesis. CEP adducts activate toll-like receptor 2, are elevated in AMD Bruch’s membrane/RPE/choroid and AMD plasma, and stimulate neovascularization independent of VEGF. Mice immunized with CEP develop an AMD-like phenotype. Photoxidation of RPE lipofuscin can result in activation of complement and generation of advanced glycation end products. Mounting evidence implicates oxidative modifications as triggers and catalysts of inflammatory and immune responses in AMD pathology.KeywordsVascular Endothelial Growth FactorRetinal Pigment EpitheliumRetinal Pigment Epithelium CellOxidative ModificationGeographic AtrophyThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves." @default.
- W52700281 created "2016-06-24" @default.
- W52700281 creator A5068769791 @default.
- W52700281 date "2012-01-01" @default.
- W52700281 modified "2023-09-23" @default.
- W52700281 title "Oxidative Modifications as Triggers of AMD Pathology" @default.
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