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.

scholarly journals The role of genetically determined factors in age-related macular degeneration pathogenesis

2015 ◽  
Vol 8 (4) ◽  
pp. 30-39
Author(s):  
Svetlana Georgievna Belekhova ◽  
Yury Sergeevich Astakhov
Keyword(s):  
Macular Degeneration ◽  
Genetic Factors ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Age Related ◽  
Genetically Determined

The article presents a review of studies dedicated to the role of genetic factors in age-related macular degeneration (AMD) pathogenesis. The polymorphisms of Y402H gene of the complement factor Н, HTRA1, ARMS2/LOC387715, and PLEKHA1 increase the risk of AMD development. More detailed description is done also for other genes, involved into this disease, which were identified so far. Possible schemes of influence of mutations in these genes on AMD development and progression

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 Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration

2020 ◽  
Vol 11 ◽  
Author(s):  
Matteo Stravalaci ◽  
Francesca Davi ◽  
Raffaella Parente ◽  
Marco Gobbi ◽  
Barbara Bottazzi ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Complement Activation ◽  
Hot Spot ◽  
Alternative Pathway ◽  
Retinal Pigment ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Rpe Cells ◽  
Age Related

Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the complement factor H (CFH) gene; factor H (FH) is the major inhibitor of the alternative pathway (AP) of complement that specifically targets C3b and the AP C3 convertase. Long pentraxin 3 (PTX3) is a soluble pattern recognition molecule that has been proposed to inhibit AP activation via recruitment of FH. Although present in the human retina, if and how PTX3 plays a role in AMD is still unclear. In this work we demonstrated the presence of PTX3 in the human vitreous and studied the PTX3-FH-C3b crosstalk and its effects on complement activation in a model of retinal pigment epithelium (RPE). RPE cells cultured in inflammatory AMD-like conditions overexpressed the PTX3 protein, and up-regulated AP activating genes. PTX3 bound RPE cells in a physiological setting, however this interaction was reduced in inflammatory conditions, whereby PTX3 had no complement-inhibiting activity on inflamed RPE. However, on non-cellular surfaces, PTX3 formed a stable ternary complex with FH and C3b that acted as a “hot spot” for complement inhibition. Our findings suggest a protective role for PTX3 in response to complement dysregulation in AMD and point to a novel mechanism of complement regulation by this pentraxin with potential implications in pathology and pharmacology of AMD.

scholarly journals Factors determining age-related macular degeneration: a current view

Medicina ◽  
2010 ◽  
Vol 46 (2) ◽  
pp. 89 ◽  
Author(s):  
Rasa Liutkevičienė ◽  
Vaiva Lesauskaitė ◽  
Virginija Ašmonienė ◽  
Dalia Žaliūnienė ◽  
Vytautas Jašinskas
Keyword(s):  
Matrix Metalloproteinases ◽  
Macular Degeneration ◽  
Visual Loss ◽  
Genetic Factors ◽  
Proteolytic Enzymes ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Age Related ◽  
Apo E

Age-related macular degeneration affects the macula and is the leading cause of significant and irreversible central visual loss. It is the most common cause of visual loss in people older than 60 years. The pathogenesis of age-related macular degeneration is complex and not completely understood. It is thought that age-related macular degeneration has a multifactorial etiology, the development of which may be caused by interrelation of environmental and genetic factors and body characteristics. In this article, risk factors such as age, gender, cigarette smoking, color of the iris, nutrition, body mass index, oxidative stress, and genetic factors (complement factor H gene, Apo E gene, and others) are reviewed. Here, choroidal neovascularization process, in which hypoxia, inflammatory process, and proteolytic enzymes play a determinant role, is discussed. Considerable attention is paid to genetic polymorphism of matrix metalloproteinases, especially to matrix metalloproteinases 2 and 9, respectively gelatinases A and B, also to matrix metalloproteinase 9.

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.

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
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