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Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator

Overview of attention for article published in Journal of Neuroinflammation, January 2017
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1 patent

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Title
Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator
Published in
Journal of Neuroinflammation, January 2017
DOI 10.1186/s12974-016-0776-3
Pubmed ID
Authors

Sven Micklisch, Yuchen Lin, Saskia Jacob, Marcus Karlstetter, Katharina Dannhausen, Prasad Dasari, Monika von der Heide, Hans-Martin Dahse, Lisa Schmölz, Felix Grassmann, Medhanie Alene, Sascha Fauser, Harald Neumann, Stefan Lorkowski, Diana Pauly, Bernhard H. Weber, Antonia M. Joussen, Thomas Langmann, Peter F. Zipfel, Christine Skerka

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The polymorphism rs10490924 in the ARMS2 gene is highly associated with AMD and linked to an indel mutation (del443ins54), the latter inducing mRNA instability. At present, the function of the ARMS2 protein, the exact cellular sources in the retina and the biological consequences of the rs10490924 polymorphism are unclear. Recombinant ARMS2 was expressed in Pichia pastoris, and protein functions were studied regarding cell surface binding and complement activation in human serum using fluoresence-activated cell sorting (FACS) as well as laser scanning microscopy (LSM). Biolayer interferometry defined protein interactions. Furthermore, endogenous ARMS2 gene expression was studied in human blood derived monocytes and in human induced pluripotent stem cell-derived microglia (iPSdM) by PCR and LSM. The ARMS2 protein was localized in human genotyped retinal sections and in purified monocytes derived from AMD patients without the ARMS2 risk variant by LSM. ARMS2 expression in monocytes under oxidative stress was determined by Western blot analysis. Here, we demonstrate for the first time that ARMS2 functions as surface complement regulator. Recombinant ARMS2 binds to human apoptotic and necrotic cells and initiates complement activation by recruiting the complement activator properdin. ARMS2-properdin complexes augment C3b surface opsonization for phagocytosis. We also demonstrate for the first time expression of ARMS2 in human monocytes especially under oxidative stress and in microglia cells of the human retina. The ARMS2 protein is absent in monocytes and also in microglia cells, derived from patients homozygous for the ARMS2 AMD risk variant (rs10490924). ARMS2 is likely involved in complement-mediated clearance of cellular debris. As AMD patients present with accumulated proteins and lipids on Bruch's membrane, ARMS2 protein deficiency due to the genetic risk variant might be involved in drusen formation.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 84 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 84 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 20%
Researcher 16 19%
Student > Bachelor 13 15%
Other 9 11%
Student > Master 9 11%
Other 10 12%
Unknown 10 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 25%
Medicine and Dentistry 16 19%
Agricultural and Biological Sciences 8 10%
Neuroscience 8 10%
Immunology and Microbiology 7 8%
Other 10 12%
Unknown 14 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 March 2022.
All research outputs
#6,305,920
of 21,347,849 outputs
Outputs from Journal of Neuroinflammation
#1,038
of 2,457 outputs
Outputs of similar age
#123,593
of 391,592 outputs
Outputs of similar age from Journal of Neuroinflammation
#2
of 5 outputs
Altmetric has tracked 21,347,849 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 2,457 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 57% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 391,592 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.