Risk Factors and Genetics in Wet-Form (Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 167-172
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Complex Disease ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Genetic Knowledge ◽  
Complement Factor ◽  
Epigenetic Factors ◽  
Age Related

Age-related macular degeneration (AMD) is a complex disease, with both genetic and environmental risk factors. Epigenetic factors also seem to play a role in the pathogenesis of AMD. Current genetic knowledge has brought opportunities for improved risk assessment and diagnosis of genetic variants. Complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) are the most studied genes associated with AMD. A better understanding of the role of genetics in AMD may lead to personalized treatment in the future.

scholarly journals The Role of Complement in Age-Related Macular Degeneration: Heparan Sulphate, a ZIP Code for Complement Factor H?

2013 ◽  
Vol 6 (4) ◽  
pp. 407-416 ◽  
Author(s):  
Alex Langford-Smith ◽  
Tiarnan D.L. Keenan ◽  
Simon J. Clark ◽  
Paul N. Bishop ◽  
Anthony J. Day
Keyword(s):  
Macular Degeneration ◽  
Heparan Sulphate ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Complement Factor ◽  
Age Related ◽  
Zip Code

scholarly journals Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 763
Author(s):  
Sara Romero-Vazquez ◽  
Víctor Llorens ◽  
Alba Soler-Boronat ◽  
Marc Figueras-Roca ◽  
Alfredo Adan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Macular Degeneration ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Low Grade ◽  
Complement Factor ◽  
Age Related ◽  
And Oxidative Stress

Age-related macular degeneration (AMD) heads the list of legal blindness among the elderly population in developed countries. Due to the complex nature of the retina and the variety of risk factors and mechanisms involved, the molecular pathways underlying AMD are not yet fully defined. Persistent low-grade inflammation and oxidative stress eventually lead to retinal pigment epithelium dysfunction and outer blood–retinal barrier (oBRB) breakdown. The identification of AMD susceptibility genes encoding complement factors, and the presence of inflammatory mediators in drusen, the hallmark deposits of AMD, supports the notion that immune-mediated processes are major drivers of AMD pathobiology. Complement factor H (FH), the main regulator of the alternative pathway of the complement system, may have a key contribution in the pathogenesis of AMD as it is able to regulate both inflammatory and oxidative stress responses in the oBRB. Indeed, genetic variants in the CFH gene account for the strongest genetic risk factors for AMD. In this review, we focus on the roles of inflammation and oxidative stress and their connection with FH and related proteins as regulators of both phenomena in the context of AMD.

scholarly journals The role of complement system and other inflammatory factors in the development of age-related macular degeneration

2018 ◽  
Vol 99 (4) ◽  
pp. 657-664
Author(s):  
E A Abdulaeva
Keyword(s):  
Macular Degeneration ◽  
Complement System ◽  
Genetic Factors ◽  
Alternative Pathway ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Inflammatory Factors ◽  
Complement Factor ◽  
Age Related

The article is a review of literature on the role of complement system and inflammatory factors in the development of age-related macular degeneration. The review uses materials of domestic and foreign researchers. The clinical characteristics of age-related macular degeneration are presented, the role of genetic factors, complement factors, biomarkers of inflammation and alternative pathway of complement activation in the pathogenesis and risk of age-related macular degeneration is determined. Age-related macular degeneration is a chronic progressive multifactorial disease that affects macular area of the retina and is the main cause of loss of central vision in patients of older age group. The most important genetic factors are chromosome 1 (1q32) including complement factor H and complement factor H related genes and chromosome 10 (10q31). Variants associated with a moderate effect on developmental risk were identified in C3, complement factor I and complement factor B genes. In the pathogenesis of age-related macular degeneration, the key role is played by the damaged regulation of the alternative complement pathway. Single nucleotide polymorphisms in complement genes that affect the risk of development of age-related macular degeneration are predominantly involved in the alternative pathway of activation of the complement system. In pathomorphological studies, the initial localization of the pathological process of this pathology was established to be a complex of retinal pigment epithelium, Bruch’s membrane, and choriocapillaries followed by loss of photoreceptor function. The review of studies of systemic inflammatory biomarkers, cytokines, vascular endothelial growth factors in peripheral blood, blood serum, aqueous humour at various stages and forms of age-related macular degeneration is presented.

Complement factor H R1210C among Japanese patients with age-related macular degeneration

2015 ◽  
Vol 59 (5) ◽  
pp. 273-278 ◽  
Author(s):  
Masahiro Miyake ◽  
Masaaki Saito ◽  
Kenji Yamashiro ◽  
Tetsuju Sekiryu ◽  
Nagahisa Yoshimura
Keyword(s):  
Macular Degeneration ◽  
Japanese Patients ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Complement Factor ◽  
Age Related

scholarly journals Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 622
Author(s):  
Iswariyaraja Sridevi Gurubaran ◽  
Hanna Heloterä ◽  
Stephen Marry ◽  
Ali Koskela ◽  
Juha M. T. Hyttinen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Macular Degeneration ◽  
Complement Component ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Complement Factor ◽  
Age Related ◽  
Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

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