title: Age-related macular degeneration and the role of the complement system.
abstract: Age-related macular degeneration (AMD) is a leading cause of visual impairment. It is characterised by damage to a tissue complex composed of the retinal pigment epithelium, Bruch's membrane and choriocapillaris. In early AMD extracellular debris including drusen accumulates in Bruch's membrane and then in late AMD geographic atrophy and/or neovascularisation develop. Variants in genes encoding components of the alternative pathway of the complement cascade have a major influence on AMD risk, especially at the RCA locus on chromosome 1, which contains CFH and the CFHR genes. Immunohistochemical studies have demonstrated complement components in unaffected and AMD macular tissue. Whilst other factors, including oxidative stress, play important roles in AMD pathogenesis, evidence for the central role played by complement dysregulation is discussed in this review.
authors: Centre for Ophthalmology & Vision Sciences, Institute of Human Development, University of Manchester, Manchester, UK; Centre for Advanced Discovery & Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: Selina
authors: S
authors: McHarg
authors: Centre for Ophthalmology & Vision Sciences, Institute of Human Development, University of Manchester, Manchester, UK; Centre for Advanced Discovery & Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: Simon J
authors: SJ
authors: Clark
authors: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors: Anthony J
authors: AJ
authors: Day
authors: Centre for Ophthalmology & Vision Sciences, Institute of Human Development, University of Manchester, Manchester, UK; Centre for Advanced Discovery & Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. Electronic address: Paul.Bishop@Manchester.ac.uk.
authors: Paul N
authors: PN
authors: Bishop
mesh_terms: D016570:Bruch Membrane / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D002878:Chromosomes, Human, Pair 1; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins / Q000235:genetics / Q000276:immunology*; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D018384:Oxidative Stress; D055213:Retinal Pigment Epithelium / Q000737:chemistry / Q000276:immunology / Q000473:pathology*
chemical_list: C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H
keywords: Age-related macular degeneration; Alternative pathway; Complement system