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

Arthur A. Bergen, Swati Arya, C. line Koster, Matthew G. Pilgrim, Dagmara Wiatrek-Moumoulidis, Peter J. van der Spek, Stefanie M. Hauck, Camiel J. F. Boon, Eszter Emri, Alan J. Stewart, Imre Lengyel

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)55-84
JournalProgress in Retinal and Eye Research
Volume70
DOIs
Publication statusPublished - 1 May 2019
Externally publishedYes

Cite this

Bergen, A. A., Arya, S., Koster, C. L., Pilgrim, M. G., Wiatrek-Moumoulidis, D., van der Spek, P. J., ... Lengyel, I. (2019). On the origin of proteins in human drusen: The meet, greet and stick hypothesis. Progress in Retinal and Eye Research, 70, 55-84. https://doi.org/10.1016/j.preteyeres.2018.12.003