title: Immunohistochemical localization of complement regulatory proteins in the human retina.
abstract: Age-related macular degeneration (AMD) is a complex disease. Genetic studies have found strong associations between AMD and variants of several complement pathway-associated genes. The regulation of the complement cascade seems to be critical in the pathogenesis of AMD. In 45 human donor eyes immunohistochemistry was performed using antibodies directed against major regulators of the complement system: complement factor H (CFH), decay accelerating factor (DAF/CD55), complement receptor 1 (CR1/CD35), and membrane cofactor protein (MCP/CD46). All eyes were classified in AMD and controls. 11 eyes were graded as early AMD. 34 eyes were controls. In all eyes staining was found in intercapillary pillars of choroid adjacent to Bruch's membrane for CFH, at the basal surface of RPE cells for MCP, and at the apical side of the retinal pigment epithelium for CR1. DAF immunoreactivity was increased along the inner segments of rod and cone photoreceptor cells at the level of the external limiting membrane Labeling of soft drusen was found for CFH and CR1. In addition, DAF and CR1 showed staining of ganglion cells in all eyes. CFH and particularly MCP showed decreased or absent staining in eyes with early AMD adjacent to Bruch's membrane. The overlapping expression of regulators at the level of Bruch's membrane and the retinal pigment epithelium shows the importance of this site for control of the complement system. Decreased and therefore unbalanced expression of regulators, as shown in this study for CFH and MCP, may ultimately lead to AMD.
authors.affiliation: Center of Ophthalmology, University of Cologne, Cologne, Germany.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Fett
authors.forename: Manuel M
authors.initials: MM
authors.lastname: Hermann
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Muether
authors.forename: Bernd
authors.initials: B
authors.lastname: Kirchhof
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D000328:Adult; D000368:Aged; D018958:CD55 Antigens / Q000032:analysis; D016022:Case-Control Studies; D017242:Complement Factor H / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis*; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000276:immunology* / Q000473:pathology; D051916:Membrane Cofactor Protein / Q000032:analysis; D008875:Middle Aged; D017463:Receptors, Complement 3b / Q000032:analysis; D012160:Retina / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult
chemical_list: C497857:CD46 protein, human; D018958:CD55 Antigens; C493495:CFH protein, human; C509991:CR1 protein, human; D051916:Membrane Cofactor Protein; D017463:Receptors, Complement 3b; D017242:Complement Factor H; D003165:Complement System Proteins