Age-related macular degeneration and the complement system

• Published in: Immunobiology (1979) Vol. 217; no. 2; pp. 127 - 146
• Main Authors: Khandhadia, S, Cipriani, V, Yates, J.R.W, Lotery, A.J
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.02.2012
• Subjects: Advanced Basic Science; Age Factors; Allergy and Immunology; Alternative/genetics; Blindness - etiology; Complement Activation - immunology; Complement factor H/genetics; Complement Inactivator Proteins - therapeutic use; Complement pathway; Complement System Proteins - genetics; Complement System Proteins - metabolism; Humans; Immunogenetic phenomena; Inflammation/genetics; Inflammation/immunology; Macular Degeneration - complications; Macular Degeneration - genetics; Macular Degeneration - immunology; Macular Degeneration - pathology; Oxidative Stress; Polymorphism; Proteins/genetics; Retina - immunology; Retina - pathology; Single nucleotide; FFA; complement receptor 1, complement receptor 2; OCT; C-reactive protein; SCR; choroidal neovascularisation; geographic atrophy; single nucleotide polymorphism; Humans; Alternative/genetics; CR1, CR2; odds ratio; short consensual repeat; Proteins/genetics; membrane cofactor protein, or CD46; AMD; Single nucleotide; age-related macular degeneration; linkage disequilibrium; Macular degeneration/genetics; complement factor D; complement factor B; decay accelerating factor, or CD55; NV AMD; CEP; CFHR; Age-Related Eye Disease Study; TCC; carboxyethylpyrrole; choroidalneovascular membrane; complement C1, complement C2, etc; complement factor I; CFB; complement factor H; ELISA; CFD; CRP; neovascular (wet) AMD; N/A; CFH; photodynamic therapy; RPE; CFI; CNV; Complement pathway; BM; Complement factor H/genetics; C1, C2, etc; Inflammation/immunology; Chlamydia Pneumoniae; SNP; reference SNP number (as allocated by the SNP database of the National Centre of Biotechnology Information-NCBI); Immunogenetic phenomena; not available; Inflammation/genetics; GA; retinal pigment epithelium; CFH-related; PDT; Rs; OR; VEGF; DAF; Bruch's membrane; CP; optical coherence tomogram; vascular endothelial growth factor; Macular degeneration/immunology; enzyme-linked immunosorbent assay; fundus fluorescein angiogram; LD; AREDS; Complement system proteins/genetics; MCP; CNVM; terminal complement complex; Polymorphism
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2011.07.019

Abstract Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a complex multifactorial disease, and despite new advances in treatment, many patients still succumb to visual impairment. The complement pathway has been implicated in the pathogenesis of many diseases, and recently variants in several genes encoding complement pathway proteins have been associated with AMD. Complement proteins have been found in histological specimens of eyes with AMD. Altered levels of both intrinsic complement proteins and activated products have been found in the circulation of patients with AMD. Complement activation may be triggered by oxidative stress, resulting from retinal exposure to incoming light; indeed an inter-play between these two pathological processes seems to exist. Finally, complement inhibitors are currently being evaluated in clinical trials. This article reviews the role of the complement system in AMD, and the potential of complement inhibition in preventing the devastating blindness resulting from this disease.