Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation)

• Published in: Mediators of Inflammation Vol. 2014; no. 9; pp. 326 - 335
• Main Authors: Huerva, Valentín, Ascaso, Francisco J., Grzybowski, Andrzej, Nita, Małgorzata
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01-01-2014; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Aging; Autoantibodies - metabolism; C-reactive protein; Chemokines; Chronic illnesses; Complement Factor H - metabolism; Cytokines; Genetic aspects; Genetic polymorphisms; Health aspects; Homeostasis; Humans; Identification and classification; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Macular degeneration; Macular Degeneration - immunology; Macular Degeneration - metabolism; Macular Degeneration - pathology; Oxidative stress; Pathogenesis; Photoreceptors; Physiology; Review; Vascular endothelial growth factor
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2014/930671

The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation) process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH) and facilitates chronic inflammation mediated by C-reactive protein (CRP). Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2) and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages); however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages).