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On the origin of proteins in human drusen: The meet, greet and stick hypothesis
Open accessAbstract
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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“drusen, a hallmark of AMD containing systemic proteins, have been suggested to result from pathological transport of visual cycle by-products across the capillary wall or BrM [219].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [219]
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Central serous chorioretinopathy: Towards an evidence-based treatment guideline
van Rijssen, T. J., van Dijk, E. H. C., Yzer, S., Ohno‐Matsui, K., KEUNEN, J. E. E., Schlingemann, R. O., Sivaprasad, S., Querques, G., Downes, S. M., Fauser, S., et al. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.07.003 · Cited by 489
Self-citationFields, M. A., Priore, L. V. D., Adelman, R. A., & Rizzolo, L. J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100803 · Cited by 179
Retinal Degeneration and Alzheimer’s Disease: An Evolving Link
Ashok, A., Singh, N., Chaudhary, S., Bellamkonda, V., Kritikos, A. E., Wise, A. S., Rana, N. A., McDonald, D., & Ayyagari, R. V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197290 · Cited by 164
Schnichels, S., Paquet‐Durand, F., Löscher, M., Tsai, T., Hurst, J., Joachim, S. C., & Klettner, A. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100880 · Cited by 152
Central serous chorioretinopathy: An evidence-based treatment guideline
Feenstra, H. M. A., van Dijk, E. H. C., Cheung, C. M. G., Ohno‐Matsui, K., Lai, T. Y. Y., Koizumi, H., Larsen, M., Querques, G., Downes, S. M., Yzer, S., et al. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101236 · Cited by 141
Self-citation
Metadata
- Authors
- Bergen, A. A., Arya, S., Koster, C., Pilgrim, M. G., Wiatrek-Moumoulidis, D., van der Spek, P. J., Hauck, S. M., Boon, C. J. F., Emri, E., Stewart, A. J., & Lengyel, I.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- University of St Andrews (GB)
- Amsterdam UMC Location University of Amsterdam (NL)
- University College London (GB)
- Helmholtz Munich (DE)
- Leiden University Medical Center (NL)
- Queen's University Belfast (GB)
- Corresponding author
- Bergen, Arthur A.
- ORCID
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 70
- Pages
- 55-84
- ISSN
- 1350-9462 (ISSN-L)
- OpenAlex
- W2905434803
- Cited by
- 101
- References
- 303
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 17 · 2023: 18 · 2022: 15 · 2021: 17 · 2020: 18 · 2019: 7
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- St Andrews Research Repository (St Andrews Research Repository) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- de Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB)
- de Stichting Blinden-Penning
- de Gelderse Blinden Stichting
- de Landelijke Stichting voor Blinden en Slechtzienden (LSBS)
- Stichting Oogfonds Nederland
- Stichting MD Fonds
- Stichting Retina Nederland Fonds
- Uitzicht (2011-6, 2014-7)
- de Rotterdamse Stichting Blindenbelangen (RSB)
- de Haagse Stichting Blindenhulp
- Stichting Lijf en Leven
- Stichting voor Ooglijders
- ZonMW (446001002)
- Bill Brown Charitable Trust
- Moorfields Eye Hospital Special Trustees
- Fight for Sight
- European Union’s Horizon 2020 research and innovation programme (634479)
- Bright Focus Foundation (M2015370)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- retinal drusen, age-related macular degeneration, retinal pigment epithelium, photoreceptor outer segments, choroid, drusen formation, Alzheimer's disease, kidney disease
- MeSH terms
- Eye Proteins, Humans, Retinal Drusen, Bruch Membrane, Proteome, Proteomics, Retinal Pigment Epithelium
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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