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

被引:78
作者
Bergen, Arthur A. [1 ,2 ,3 ]
Arya, Swati [4 ]
Koster, Celine [1 ]
Pilgrim, Matthew G. [5 ]
Wiatrek-Moumoulidis, Dagmara [4 ,6 ]
van der Spek, Peter J. [7 ]
Hauck, Stefanie M. [8 ]
Boon, Camiel J. F. [2 ,9 ]
Emri, Eszter [10 ]
Stewart, Alan J. [4 ]
Lengyel, Imre [5 ,10 ]
机构
[1] Univ Amsterdam, Dept Clin Genet, Amsterdam UMC, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Dept Ophthalmol, Amsterdam UMC, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
[3] NIN, KNAW, Amsterdam, Netherlands
[4] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland
[5] UCL, Inst Ophthalmol, London, England
[6] UCL, Eastman Dent Inst, Div Biomat & Tissue Engn, London, England
[7] Erasmus MC, Div Clin Bioinformat, Dept Pathol, Rotterdam, Netherlands
[8] German Res Ctr Environm Hlth GmbH, Res Unit Prot Sci, Helmholtz Zentrum Munchen, Neuherberg, Germany
[9] Leiden Univ, Dept Ophthalmol, Med Ctr, Leiden, Netherlands
[10] Queens Univ, Sch Med Dent & Biomed Sci, Ctr Expt Med, Belfast, Antrim, North Ireland
基金
欧盟地平线“2020”;
关键词
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;
D O I
10.1016/j.preteyeres.2018.12.003
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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.
引用
收藏
页码:55 / 84
页数:30
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