scholarly journals Semi-Quantitative Multiplex Profiling of the Complement System Identifies Associations of Complement Proteins with Genetic Variants and Metabolites in Age-Related Macular Degeneration

2021 ◽  
Vol 11 (12) ◽  
pp. 1256
Author(s):  
I. Erkin Acar ◽  
Esther Willems ◽  
Eveline Kersten ◽  
Jenneke Keizer-Garritsen ◽  
Else Kragt ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Complement System ◽  
Genetic Variants ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Protein ◽  
Complement Proteins ◽  
New Associations ◽  
Age Related ◽  
The Complement System

Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. The complement system has been identified as one of the main AMD disease pathways. We performed a comprehensive expression analysis of 32 complement proteins in plasma samples of 255 AMD patients and 221 control individuals using mass spectrometry-based semi-quantitative multiplex profiling. We detected significant associations of complement protein levels with age, sex and body-mass index (BMI), and potential associations of C-reactive protein, factor H related-2 (FHR-2) and collectin-11 with AMD. In addition, we confirmed previously described associations and identified new associations of AMD variants with complement levels. New associations include increased C4 levels for rs181705462 at the C2/CFB locus, decreased vitronectin (VTN) levels for rs11080055 at the TMEM97/VTN locus and decreased factor I levels for rs10033900 at the CFI locus. Finally, we detected significant associations between AMD-associated metabolites and complement proteins in plasma. The most significant complement-metabolite associations included increased high density lipoprotein (HDL) subparticle levels with decreased C3, factor H (FH) and VTN levels. The results of our study indicate that demographic factors, genetic variants and circulating metabolites are associated with complement protein components. We suggest that these factors should be considered to design personalized treatment approaches and to increase the success of clinical trials targeting the complement system.

scholarly journals Genetic variants in the complement system predisposing to age-related macular degeneration: A review

2014 ◽  
Vol 61 (2) ◽  
pp. 118-125 ◽  
Author(s):  
Elizabeth C. Schramm ◽  
Simon J. Clark ◽  
Michael P. Triebwasser ◽  
Soumya Raychaudhuri ◽  
Johanna M. Seddon ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Complement System ◽  
Genetic Variants ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Complement System

scholarly journals Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 635
Author(s):  
Monica L. Hu ◽  
Joel Quinn ◽  
Kanmin Xue
Keyword(s):  
Risk Factor ◽  
Apolipoprotein E ◽  
Macular Degeneration ◽  
Amyloid Beta ◽  
Complement System ◽  
Genetic Risk ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Inflammation ◽  
The Complement System

Age-related macular degeneration (AMD) is a multifactorial retinal disorder that is a major global cause of severe visual impairment. The development of an effective therapy to treat geographic atrophy, the predominant form of AMD, remains elusive due to the incomplete understanding of its pathogenesis. Central to AMD diagnosis and pathology are the hallmark lipid and proteinaceous deposits, drusen and reticular pseudodrusen, that accumulate in the subretinal pigment epithelium and subretinal spaces, respectively. Age-related changes and environmental stressors, such as smoking and a high-fat diet, are believed to interact with the many genetic risk variants that have been identified in several major biochemical pathways, including lipoprotein metabolism and the complement system. The APOE gene, encoding apolipoprotein E (APOE), is a major genetic risk factor for AMD, with the APOE2 allele conferring increased risk and APOE4 conferring reduced risk, in comparison to the wildtype APOE3. Paradoxically, APOE4 is the main genetic risk factor in Alzheimer's disease, a disease with features of neuroinflammation and amyloid-beta deposition in common with AMD. The potential interactions of APOE with the complement system and amyloid-beta are discussed here to shed light on their roles in AMD pathogenesis, including in drusen biogenesis, immune cell activation and recruitment, and retinal inflammation.

scholarly journals Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Maria Grazia Mazzone ◽  
Francesco Giuliano ◽  
Antonella Agodi
Keyword(s):  
Public Health ◽  
Personalized Medicine ◽  
Macular Degeneration ◽  
Complement System ◽  
Genetic Variants ◽  
Age Related Macular Degeneration ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Age Related ◽  
Gene Environment

Age-related macular degeneration (AMD) is the most common cause of visual loss in developed countries, with a significant economic and social burden on public health. Although genome-wide and gene-candidate studies have been enabled to identify genetic variants in the complement system associated with AMD pathogenesis, the effect of gene-environment interaction is still under debate. In this review we provide an overview of the role of complement system and its genetic variants in AMD, summarizing the consequences of the interaction between genetic and environmental risk factors on AMD onset, progression, and therapeutic response. Finally, we discuss the perspectives of current evidence in the field of genomics driven personalized medicine and public health.

Age-related macular degeneration and the complement system

Immunobiology ◽  
2012 ◽  
Vol 217 (2) ◽  
pp. 127-146 ◽  
Author(s):  
S. Khandhadia ◽  
V. Cipriani ◽  
J.R.W. Yates ◽  
A.J. Lotery
Keyword(s):  
Macular Degeneration ◽  
Complement System ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Complement System

scholarly journals Complement System and Potential Therapeutics in Age-Related Macular Degeneration

2021 ◽  
Vol 22 (13) ◽  
pp. 6851
Author(s):  
Young-Gun Park ◽  
Yong-Soo Park ◽  
In-Beom Kim
Keyword(s):  
Macular Degeneration ◽  
Complement System ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelium Cell ◽  
Immune Surveillance ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Complement System

Age-related macular degeneration (AMD) is a complex multifactorial disease characterized in its late form by neovascularization (wet type) or geographic atrophy of the retinal pigment epithelium cell layer (dry type). The complement system is an intrinsic component of innate immunity. There has been growing evidence that the complement system plays an integral role in maintaining immune surveillance and homeostasis in AMD. Based on the association between the genotypes of complement variants and AMD occurrence and the presence of complement in drusen from AMD patients, the complement system has become a therapeutic target for AMD. However, the mechanism of complement disease propagation in AMD has not been fully understood. This concise review focuses on an overall understanding of the role of the complement system in AMD and its ongoing clinical trials. It provides further insights into a strategy for the treatment of AMD targeting the complement system.

scholarly journals Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Denise C. Zysset-Burri ◽  
Irene Keller ◽  
Lieselotte E. Berger ◽  
Carlo R. Largiadèr ◽  
Matthias Wittwer ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Complement System ◽  
Age Related Macular Degeneration ◽  
Intestinal Microbiome ◽  
Age Related ◽  
The Complement System
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