High concentration of zinc in sub-retinal pigment epithelial deposits

Imre Lengyel; Jane M. Flinn; Tünde Peto; David H. Linkous; Katherine Cano; Alan C. Bird; Antonio Lanzirotti; Christopher J. Frederickson; Frederik J.G.M. van Kuijk

doi:10.1016/j.exer.2006.12.015

High concentration of zinc in sub-retinal pigment epithelial deposits

Imre Lengyel, Jane M. Flinn, Tünde Peto, David H. Linkous, Katherine Cano, Alan C. Bird, Antonio Lanzirotti, Christopher J. Frederickson, Frederik J.G.M. van Kuijk

Ophthalmology & Visual Neurosciences

Research output: Contribution to journal › Article › peer-review

117 Scopus citations

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.

Original language	English (US)
Pages (from-to)	772-780
Number of pages	9
Journal	Experimental Eye Research
Volume	84
Issue number	4
DOIs	https://doi.org/10.1016/j.exer.2006.12.015
State	Published - Apr 2007

Bibliographical note

Funding Information:
We thank Bill Rao and Dr. Paul Northrup for help with μSXRF, and Dr. Peter Munro, Dr. Blair Jones, Dr. Leonard Giblin III and Dr. Cathy Frederickson for their generous help. We are thankful for Dr. Philip J. Luthert, Dr. Mike Boulton and Dr. Stephen J. Perkins for their helpful comments. This study was supported by a BNL general user grant; Financial Assistance Award DE-FC09-96R18546 (J.M.F.); DOE grant DE-FG02-92ER14244; the U.S. Department of Energy under Contract No. DEAC02-76CH00016. The research was supported by OTKA (T037911), Moorfields Eye Hospital Special Trustees and Mercer Fund from Fight for Sight (I.L.) and Wilkins AMD fund (FJGMvK).

Keywords

Bruch's membrane
age-related macular degeneration
complement factor H
drusen
retinal pigment epithelium
sub-RPE deposit
trace element
zinc

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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.",

keywords = "Bruch's membrane, age-related macular degeneration, complement factor H, drusen, retinal pigment epithelium, sub-RPE deposit, trace element, zinc",

author = "Imre Lengyel and Flinn, {Jane M.} and T{\"u}nde Peto and Linkous, {David H.} and Katherine Cano and Bird, {Alan C.} and Antonio Lanzirotti and Frederickson, {Christopher J.} and {van Kuijk}, {Frederik J.G.M.}",

note = "Funding Information: We thank Bill Rao and Dr. Paul Northrup for help with μSXRF, and Dr. Peter Munro, Dr. Blair Jones, Dr. Leonard Giblin III and Dr. Cathy Frederickson for their generous help. We are thankful for Dr. Philip J. Luthert, Dr. Mike Boulton and Dr. Stephen J. Perkins for their helpful comments. This study was supported by a BNL general user grant; Financial Assistance Award DE-FC09-96R18546 (J.M.F.); DOE grant DE-FG02-92ER14244; the U.S. Department of Energy under Contract No. DEAC02-76CH00016. The research was supported by OTKA (T037911), Moorfields Eye Hospital Special Trustees and Mercer Fund from Fight for Sight (I.L.) and Wilkins AMD fund (FJGMvK).",

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AU - Lengyel, Imre

AU - Flinn, Jane M.

AU - Peto, Tünde

AU - Linkous, David H.

AU - Cano, Katherine

AU - Bird, Alan C.

AU - Lanzirotti, Antonio

AU - Frederickson, Christopher J.

AU - van Kuijk, Frederik J.G.M.

N1 - Funding Information: We thank Bill Rao and Dr. Paul Northrup for help with μSXRF, and Dr. Peter Munro, Dr. Blair Jones, Dr. Leonard Giblin III and Dr. Cathy Frederickson for their generous help. We are thankful for Dr. Philip J. Luthert, Dr. Mike Boulton and Dr. Stephen J. Perkins for their helpful comments. This study was supported by a BNL general user grant; Financial Assistance Award DE-FC09-96R18546 (J.M.F.); DOE grant DE-FG02-92ER14244; the U.S. Department of Energy under Contract No. DEAC02-76CH00016. The research was supported by OTKA (T037911), Moorfields Eye Hospital Special Trustees and Mercer Fund from Fight for Sight (I.L.) and Wilkins AMD fund (FJGMvK).

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N2 - 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.

AB - 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.

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KW - trace element

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EP - 780

JO - Experimental Eye Research

JF - Experimental Eye Research

IS - 4

ER -

High concentration of zinc in sub-retinal pigment epithelial deposits

Abstract

Bibliographical note

Keywords

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