Systemic Complement Activation in Age-Related Macular Degeneration

• DOI: 10.1371/journal.pone.0002593
• Publication Date: 2008-07-01T18:38:49Z
• Authors: Hendrik P. N. Scholl; Peter Charbel Issa; Maja Walier; Stefanie Janzer; Beatrix Pollok-Kopp; Florian Börncke; Lars G. Fritsche; Ngaihang V. Chong; Rolf Fimmers; Thomas Wienker; Frank G. Holz; Bernhard H. F. Weber; Martin Oppermann
• Keywords: Aged, 80 and over; Male; 0301 basic medicine; ddc:610; Genotype; Science; Q; R; 610 Medizin; Genetic Variation; Polymorphism, Single Nucleotide; Macular Degeneration; 03 medical and health sciences; Risk Factors; Case-Control Studies; Complement Factor H; Medicine; Humans; Female; Complement Activation; Research Article; Aged

Dysregulation of the alternative pathway (AP) complement cascade has been implicated in pathogenesis age-related macular degeneration (AMD), leading cause blindness elderly. To further test hypothesis that defective control activation underlies AMD, parameters blood plasma were determined together with disease-associated genetic markers AMD patients. Plasma concentrations products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators H D quantified patients (n = 112) controls 67). Subjects analyzed for single nucleotide polymorphisms (CFH), B-C2 (BF-C2) C3 (C3) genes which previously found to be associated AMD. All products, especially chronic Ba C3d (p<0.001), significantly elevated compared controls. Similar alterations observed D, but not C4 or H. Logistic regression analysis revealed better discriminative accuracy a model is based only on system within our study population. In both controls' patients' group, protein correlated CFH haplotypes.This first show systemic This suggests disease local manifestation at ageing macula. Furthermore, data provide evidence an association variants linked susceptibility.