Receptor for advanced glycation end products and age-related macular degeneration.

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Ophthalmology; Neurobiology & Anatomy; Biology
Creator Frederick, Jeanne M.; Baehr, Wolfgang
Other Author Howes, Kimberly A; Liu, Yang; Dunaief, Joshua L; Milam, Ann; Marks, Alexander
Title Receptor for advanced glycation end products and age-related macular degeneration.
Date 2004
Description Advanced glycation end products (AGE) exacerbate disease progression through two general mechanisms: modifying molecules and forming nondegradable aggregates, thus impairing normal cellular/tissue functions, and altering cellular function directly through receptor-mediated activation. In the present study receptor for AGE (RAGE)-mediated cellular activation was evaluated in the etiology of human retinal aging and disease. METHODS: The maculas of human donor retinas from normal eyes and eyes with early age-related macular degeneration (AMD) and advanced AMD with geographic atrophy (GA) were assayed for AGE and RAGE by immunocytochemistry. Cultured ARPE-19 cells were challenged with known ligands for RAGE, AGE, and S100B, to test for activation capacity. Immunocytochemistry, real-time RT-PCR, immunoblot analysis, and the TUNEL assay were used to determine the consequences of RPE cellular activation. RESULTS: Little to no immunolabeling for AGE or RAGE was found in photoreceptor and RPE cell layers in normal retinas. However, when small drusen were present, AGE and RAGE were identified in the RPE or both the RPE and photoreceptors. In early AMD and GA, the RPE and remnant photoreceptor cells showed intense AGE and RAGE immunolabeling. Both AGE and S100B activated cultured RPE cells, as revealed by upregulated expression of RAGE, NFkappaB nuclear translocation, and apoptotic cell death. CONCLUSIONS: Immunolocalization of RAGE in RPE and photoreceptors coincided with AGE deposits and macular disease in aged, early AMD, and GA retinas. Further, AGE stimulated RAGE-mediated activation of cultured ARPE-19 cells in a dose-dependent fashion. AGE accumulation, as occurs with normal aging and in disease, may induce receptor-mediated activation of RPE/photoreceptor cells, contributing to disease progression in the aging human retinas.
Type Text
Publisher Association for Research in Vision and Ophthalmology
Volume 45
Issue 10
First Page 3713
Last Page 3720
Subject Optic Atrophies, Hereditary; Apoptosis; Pigment Epithelium of Eye
Subject MESH Macular Degeneration; Receptors, Immunologic; Glycosylation End Products, Advanced
Language eng
Bibliographic Citation Howes KA, Liu Y, Dunaief JL, Milam A, Frederick JM, Marks A, Baehr W. (2004). Receptor for advanced glycation end products and age-related macular degeneration. Invest Ophthalmol Vis Sci, 45(10), 3713-20.
Rights Management (c) Association for Research in Vision and Ophthalmology
Format Medium application/pdf (portable document)
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CONTENTdm URL http://cdmbuntu.lib.utah.edu/cdm/ref/collection/uspace/id/584
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