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Bergen, A.A.* ; Arya, S.* ; Koster, C.* ; Pilgrim, M.G.* ; Wiatrek-Moumoulidis, D.* ; van der Spek, P.* ; Hauck, S.M. ; Boon, C.J.F.* ; Emri, E.* ; Stewart, A.J.* ; Lengyel, I.*

On the origin of proteins in human drusen: The meet, greet and stick hypothesis.

Prog. Retinal Eye Res. 70, 55-84 (2018)
Postprint DOI PMC
Open Access Green
Retinal drusen formation is not only a clinical hallmark for the development of age-related macular degeneration (AMD) but also for other disorders, such as Alzheimer's disease and renal diseases. The initiation and growth of drusen is poorly understood. Attention has focused on lipids and minerals, but relatively little is known about the origin of drusen-associated proteins and how they are retained in the space between the basal lamina of the retinal pigment epithelium and the inner collagenous layer space (sub-RPE-BL space). While some authors suggested that drusen proteins are mainly derived from cellular debris from processed photoreceptor outer segments and the RPE, others suggest a choroidal cell or blood origin.Here, we reviewed and supplemented the existing literature on the molecular composition of the retina/choroid complex, to gain a more complete understanding of the sources of proteins in drusen. These "drusenomics" studies showed that a considerable proportion of currently identified drusen proteins is uniquely originating from the blood. A smaller, but still large fraction of drusen proteins comes from both blood and/or RPE. Only a small proportion of drusen proteins is uniquely derived from the photoreceptors or choroid. We next evaluated how drusen components may "meet, greet and stick" to each other and/or to structures like hydroxyapatite spherules to form macroscopic deposits in the sub-RPE-BL space. Finally, we discuss implications of our findings with respect to the previously proposed homology between drusenogenesis in AMD and plaque formation in atherosclerosis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Drusen Proteins ; Retinal Pigment Epithelium (rpe) ; Bruch's Membrane ; Blood ; Age-related Macular Degeneration (amd) ; Alzheimer's Disease; Retinal-pigment Epithelium; Complement Factor-h; Age-related Maculopathy; Human Bruchs Membrane; C-reactive Protein; Senile Macular Degeneration; Apolipoprotein-e Gene; Basal Linear Deposit; Adult Human Retina; Extracellular Histones
Sprache
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 1350-9462
e-ISSN 1873-1635
Zeitschrift Progress in retinal and eye research
Quellenangaben Band: 70, Heft: , Seiten: 55-84 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Oxford [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-505700-001
DOI 10.1016/j.preteyeres.2018.12.003
WOS ID WOS:000472688300003
Scopus ID 85059867049
PubMed ID 30572124
Erfassungsdatum 2019-01-09
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