title: High concentration of zinc in sub-retinal pigment epithelial deposits.
abstract: One of the hallmarks of age-related macular degeneration (AMD), the leading cause of blindness in the elderly in Western societies, is the accumulation of sub-retinal pigment epithelial deposits (sub-RPE deposits), including drusen and basal laminar deposits, in Bruch's membrane (BM). The nature and the underlying mechanisms of this deposit formation are not fully understood. Because we know that zinc contributes to deposit formation in neurodegenerative diseases, we tested the hypothesis that zinc might be involved in deposit formation in AMD. Using zinc specific fluorescent probes and microprobe synchrotron X-ray fluorescence we showed that sub-RPE deposits in post-mortem human tissues contain unexpectedly high concentrations of zinc, including abundant bio-available (ionic and/or loosely protein bound) ions. Zinc accumulation was especially high in the maculae of eyes with AMD. Internal deposit structures are especially enriched in bio-available zinc. Based on the evidence provided here we suggest that zinc plays a role in sub-RPE deposit formation in the aging human eye and possibly also in the development and/or progression of AMD.
authors.affiliation: Division of Pathology, Institute of Ophthalmology, 11-43 Bath Street, University College London, and Department of Research and Development, Moorfields Eye Hospital, London EC1V 9EL, UK. i.lengyel@ucl.ac.uk
authors.forename: Imre
authors.initials: I
authors.lastname: Lengyel
authors.forename: Jane M
authors.initials: JM
authors.lastname: Flinn
authors.forename: Tünde
authors.initials: T
authors.lastname: Peto
authors.forename: David H
authors.initials: DH
authors.lastname: Linkous
authors.forename: Katherine
authors.initials: K
authors.lastname: Cano
authors.forename: Alan C
authors.initials: AC
authors.lastname: Bird
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzirotti
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Frederickson
authors.forename: Frederik J G M
authors.initials: FJ
authors.lastname: van Kuijk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001682:Biological Availability; D016570:Bruch Membrane / Q000378:metabolism; D006801:Humans; D008266:Macula Lutea / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism*; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D015593:Retinal Drusen / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D017356:Synchrotrons; D015032:Zinc / Q000032:analysis*
chemical_list: D015032:Zinc