Systemic Complement Activation in Age-Related Macular Degeneration

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

Multiple regression model showing significant predictors of MRS.

<p>Multiple regression model showing significant predictors of MRS.</p

SR = Slow reading group, NR = Normal reading group, SD = standard deviation, CST = Central Subfield Thickness, MV = Macular Volume, BCVA = Best corrected visual acuity, CS = Contrast Sensitivity, RA = Reading acuity, CPS = Critical Print Size, MRS- Maximum reading speed BCEA = Bivariate Contour Ellipse Area, pt = point, MP = Microperimetry.

<p>SR  =  Slow reading group, NR  =  Normal reading group, SD  =  standard deviation, CST  =  Central Subfield Thickness, MV  = Macular Volume, BCVA  =  Best corrected visual acuity, CS  =  Contrast Sensitivity, RA  =  Reading acuity, CPS  =  Critical Print Size, MRS- Maximum reading speed BCEA  =  Bivariate Contour Ellipse Area, pt  =  point, MP  =  Microperimetry.</p

Correlation between maximum reading speed (MRS) and other parameters.

<p>Correlation between maximum reading speed (MRS) and other parameters.</p

Location of the microperimeter points.

<p>Location of the microperimeter points.</p